International Immunology via MedWorm.com MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'International Immunology' source. Wed, 08 Feb 2012 06:42:54 +0100 Sulfatide inhibits {alpha}-galactosylceramide presentation by dendritic cells http://www.medworm.com/index.php?rid=5646575&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2F129%3Frss%3D1 Sulfatide-reactive type II NKT cells, the so-called non-invariant NKT (non-iNKT) cells, have been shown to counteract invariant NKT (iNKT) cell activity. However, the effects of sulfatide on activation of iNKT cells by α-galactocylceramide (αGC) in the context of CD1d have not been studied in detail. Therefore, we studied the blocking effect of sulfatide on αGC-induced iNKT cell activation by dendritic cells (DCs). Even in the absence of non-iNKT cells, sulfatide inhibited αGC-mediated iNKT cell activation by reducing αGC/CD1d complex formations in a dose-dependent manner. This was also confirmed in a cell-free setting using immobilized CD1d-Ig. Moreover, simultaneous injection of αGC with sulfatide decreased αGC/CD1d complex formations on DCs, acc... International Immunology journals http://www.medworm.com/rss/comments.php?id=5646575 Wed, 01 Feb 2012 05:00:00 +0100 5646575 Sublingual immunization with adenovirus F protein-based vaccines stimulates protective immunity against botulinum neurotoxin A intoxication http://www.medworm.com/index.php?rid=5646574&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2F117%3Frss%3D1 This study shows that s.l. immunization with Ad2F-based vaccines is effective in conferring protective immunity. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5646574 Wed, 01 Feb 2012 05:00:00 +0100 5646574 Histamine modulates multiple functional activities of monocyte-derived dendritic cell subsets via histamine receptor 2 http://www.medworm.com/index.php?rid=5646573&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2F107%3Frss%3D1 Expression of CD1a proteins in human monocyte-derived dendritic cells (DCs) specifies functionally distinct subsets with different inflammatory properties. Histamine is recognized as an inflammatory mediator released by various cell types including DCs. The diverse biological effects of histamine are mediated by G-protein-coupled histamine receptors (HRs), which are able to modulate the functional activities of DC subsets. The goal of the present study was to compare the expression and activity of HRs in the CD1a– and CD1a+ monocyte-derived DC subsets and to test the effects of histamine on the differentiation, activation and functional activities of these subsets. We show that H2R is present at high levels in both DC subsets, whereas H1R and H4R are expressed in a subset-specific ma... International Immunology journals http://www.medworm.com/rss/comments.php?id=5646573 Wed, 01 Feb 2012 05:00:00 +0100 5646573 HCV core and NS3 proteins manipulate human blood-derived dendritic cell development and promote Th 17 differentiation http://www.medworm.com/index.php?rid=5646572&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2F97%3Frss%3D1 In this study, we examined the effect of HCV proteins on the differentiation of human peripheral blood monocytes to dendritic cells (DCs). The HCV core (HCVc) and non-structural 3 (NS3) proteins inhibited the expression of CD1a, CD1b and DC-SIGN during monocyte differentiation to DCs, while increasing some markers characteristic of macrophages (CD14 and HLA-DR) and also PD-L1 expression. Meanwhile, HCVc and NS3 could induce differentiating monocytes to secrete IL-10. However, anti-IL-10 mAb could not reverse HCVc and NS3 inhibition of monocyte differentiation into DCs. The HCVc and NS3 proteins increased IL-6 secretion both in immature and in fully differentiated DCs and also promoted CD4+ T-cell IL-17 production. Since Th 17 cells are active in many examples of immunopathology, these effe... International Immunology journals http://www.medworm.com/rss/comments.php?id=5646572 Wed, 01 Feb 2012 05:00:00 +0100 5646572 Efficient capture of Candida albicans and zymosan by SIGNR1 augments TLR2-dependent TNF-{alpha} production http://www.medworm.com/index.php?rid=5646571&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2F89%3Frss%3D1 In this study, we explore the impact of SIGNR1 in the recognition of C. albicans/zymosan and the subsequent tumor necrosis factor (TNF)-α production using SIGNR1-transfected RAW264.7 (RAW-SIGNR1) cells and resident peritoneal macrophages. Compared with RAW-control cells, RAW-SIGNR1 cells dramatically enhanced TNF-α production upon the stimulation with heat-killed C. albicans and zymosan. Recognition of microbes via carbohydrate recognition domain (CRD) of SIGNR1 was crucial for the enhanced TNF-α production. Consistently, such an enhancement was significantly decreased by anti-SIGNR1 mAb. Laminarin, antagonistic Dectin-1 ligand, cooperated to further diminish the response, although no effect was observed by itself in RAW-SIGNR1 cells. However, it moderately reduced the re... International Immunology journals http://www.medworm.com/rss/comments.php?id=5646571 Wed, 01 Feb 2012 05:00:00 +0100 5646571 Fine-tuning of proximal TCR signaling by ZAP-70 tyrosine residues in Jurkat cells http://www.medworm.com/index.php?rid=5646570&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2F79%3Frss%3D1 Zeta-chain-associated protein kinase of 70kDa (ZAP-70) kinase is a key regulator in the early steps of TCR signaling but some aspects of its fine regulation are still unclear. From its 31 tyrosine (Y) residues, 11 phosphorylation sites have been identified, some with activator (Y315 and Y493) or inhibitory (Y292 and Y492) and others with unknown function (Y069, Y126 and Y178). In our present work, we aimed to elucidate the role of different Y residues of ZAP-70, especially those with unknown function, in calcium signaling and the autoregulation of the kinase. ZAP-70-deficient Jurkat cells (P116) were stably reconstituted with point-mutated ZAP-70 constructs where tyrosine residues 069, 126, 178, 238, 292, 315, 492 or 493 were replaced with phenylalanine (F). The anti-CD3-elicited calcium s... International Immunology journals http://www.medworm.com/rss/comments.php?id=5646570 Wed, 01 Feb 2012 05:00:00 +0100 5646570 Association of the level of IFN-{gamma} produced by T cells in response to Mycobacterium tuberculosis-specific antigens with the size of skin test indurations among individuals with latent tuberculosis in a highly tuberculosis-endemic setting http://www.medworm.com/index.php?rid=5646569&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2F71%3Frss%3D1 In conclusion, the results of this study could provide indirect evidence for the prognostic use of the QFTGIT assay for progression of Mtb infection, though prospective follow-up studies are needed to provide direct evidence. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5646569 Wed, 01 Feb 2012 05:00:00 +0100 5646569 In this issue http://www.medworm.com/index.php?rid=5646568&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F2%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5646568 Wed, 01 Feb 2012 05:00:00 +0100 5646568 Unraveling features of the natural MHC class II peptidome of skin-migrated dendritic cells http://www.medworm.com/index.php?rid=5551756&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F1%2F59%3Frss%3D1 Dendritic cells (DCs) migrating from peripheral tissues at steady state are considered the most efficient antigen-presenting cells (APCs) involved in the induction of peripheral T-cell tolerance via self-antigen presentation on MHC class II molecules. However, difficulties in obtaining sufficient numbers of such DCs have precluded previous analyses of their natural MHC class II peptidome in laboratory animals or humans. Here, we overcome this difficulty by collecting the large quantities of sheep DCs that migrate from the skin via the afferent lymphatics at steady state to the draining lymph node. We compared the repertoire of MHC class II-bound peptides from afferent lymph DCs with autologous APCs derived from peripheral blood. A large fraction of the MHC class II peptidome from skin DCs ... International Immunology journals http://www.medworm.com/rss/comments.php?id=5551756 Wed, 28 Dec 2011 05:00:00 +0100 5551756 Antibodies to HLA-E may account for the non-donor-specific anti-HLA class-Ia antibodies in renal and liver transplant recipients http://www.medworm.com/index.php?rid=5551755&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F1%2F43%3Frss%3D1 This study provides a new explanation for the presence of non-donor-specific antibodies for non-existing HLA-Ia alleles, frequently observed and correlated with survival in organ transplant recipients. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5551755 Wed, 28 Dec 2011 05:00:00 +0100 5551755 Cellular MRI as a suitable, sensitive non-invasive modality for correlating in vivo migratory efficiencies of different dendritic cell populations with subsequent immunological outcomes http://www.medworm.com/index.php?rid=5551754&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F1%2F29%3Frss%3D1 This study provides important information relevant to tracking the in vivo migration of ex vivo-prepared and stimulated DC. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5551754 Wed, 28 Dec 2011 05:00:00 +0100 5551754 B cells regulate antibody responses through the medullary remodeling of inflamed lymph nodes http://www.medworm.com/index.php?rid=5551753&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F1%2F17%3Frss%3D1 Lymph node (LN) structure is remodeled during immune responses, a process which is considered to play an important role in the regulation of immune function. To date, little attention has been paid to the remodeling of the medullary region, despite its proposed role as a niche for antibody-producing plasma cells. Here, we show that B cells mediate medullary remodeling of antigen-draining LNs during inflammation. This process occurs with kinetics similar to changes in plasma cell number and is accompanied by stromal renetworking which manifests as the segregation of B cells and plasma cells. Medullary remodeling depends on signaling via the lymphotoxin-β receptor and the presence of B cells but occurs independently of T-dependent humoral responses or other immune cell subsets including... International Immunology journals http://www.medworm.com/rss/comments.php?id=5551753 Wed, 28 Dec 2011 05:00:00 +0100 5551753 The CD40-CD40L axis and IFN-{gamma} play critical roles in Langhans giant cell formation http://www.medworm.com/index.php?rid=5551752&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F1%2F5%3Frss%3D1 The presence of Langhans giant cells (LGCs) is one of the signatures of systemic granulomatous disorders such as tuberculosis and sarcoidosis. However, the pathophysiological mechanism leading to LGC formation, especially the contribution of the T cells abundantly found in granulomas, has not been fully elucidated. To examine the role of T cells in LGC formation, a new in vitro method for the induction of LGCs was developed by co-culturing human monocytes with autologous T cells in the presence of concanavalin A (ConA). This system required close contact between monocytes and T cells, and CD4+ T cells were more potent than CD8+ T cells in inducing LGC formation. Antibody inhibition revealed that a CD40–CD40 ligand (CD40L) interaction and IFN- were essential for LGC formation, and the... International Immunology journals http://www.medworm.com/rss/comments.php?id=5551752 Wed, 28 Dec 2011 05:00:00 +0100 5551752 A tribute to Ralph M. Steinman http://www.medworm.com/index.php?rid=5551751&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F1%2F1%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5551751 Wed, 28 Dec 2011 05:00:00 +0100 5551751 In this issue http://www.medworm.com/index.php?rid=5551750&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F24%2F1%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5551750 Wed, 28 Dec 2011 05:00:00 +0100 5551750 Requirement of GATA-binding protein 3 for Il13 gene expression in IL-18-stimulated Th1 cells http://www.medworm.com/index.php?rid=5456530&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F12%2F761%3Frss%3D1 Recent reports have revealed that CD4+ Th cell subsets have the ability to alter their gene expression pattern in response to extracellular stimuli. We previously highlighted the plasticity of Th1 cells by demonstrating that Th1 cells gain the capacity to produce IL-3, IL-9, IL-13 and granulocyte macrophage colony-stimulating factor in response to antigen, IL-2 and IL-18, and based on their unique function, we designated these activated Th1 cells as ‘super Th1 cells’. However, the precise molecular mechanism underlying IL-13 production by super Th1 cells has not been elucidated. Here, we show that the GATA-binding protein 3 (Gata3) is essentially required for Il13 gene expression in super Th1 cells. Gata3 is synergistically induced in T-box expressed in T-cells (T-bet)-expressi... International Immunology journals http://www.medworm.com/rss/comments.php?id=5456530 Tue, 29 Nov 2011 05:00:00 +0100 5456530 IL-17/IFN-{gamma} double producing CD8+ T (Tc17/IFN-{gamma}) cells: A novel cytotoxic T-cell subset converted from Tc17 cells by IL-12 http://www.medworm.com/index.php?rid=5456529&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F12%2F751%3Frss%3D1 It has been reported that IFN--producing CD8+ T (Tc1) cells express cytotoxic molecules such as perforin and granzyme B to exhibit higher cytotoxicity against tumor cells compared with Tc2 cells. However, the critical role of IL-17-producing CD8+ T (Tc17)-cell subsets in tumor immunity remains unclear. Tc17 cells differentiated from naive CD8+ T cells did not possess cytotoxic molecules and exhibited no strong cytotoxicity. However, when Tc17 effector cells were further cultured with IL-12, they converted into IFN--producing Tc17 cells, which mainly consisted of IL-17/IFN- double-producing cells (Tc17/IFN-). IL-12-converted Tc17 cells also acquired cytotoxic function in addition to IFN- producibility. Moreover, they showed strong anti-tumor activity both in vitro and in vivo as well as Tc1... International Immunology journals http://www.medworm.com/rss/comments.php?id=5456529 Tue, 29 Nov 2011 05:00:00 +0100 5456529 Coenzyme A contained in mothers' milk is associated with the potential to induce atopic dermatitis http://www.medworm.com/index.php?rid=5456528&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F12%2F741%3Frss%3D1 Th2 adjuvant activity can be qualitatively and quantitatively evaluated using a mixed lymphocyte reaction and by changes in the intracellular cyclic adenosine 3',5'-monophosphate concentration, using human dendritic cells in vitro. The current study shows that mothers, whose children (n = 55) developed atopic dermatitis (AD) within 6 months after birth, often demonstrate a higher Th2 adjuvant activity in their milk, in comparison to those whose children did not develop such symptoms. Such an activity was recovered in a liquid phase of mothers' milk and was eluted as a single fraction by reversed-phase HPLC. Further analysis of this fraction by mass spectrometry showed that signals originating from a factor with a molecular weight of 767.53 are observed, exclusively in milk with a high Th2 ... International Immunology journals http://www.medworm.com/rss/comments.php?id=5456528 Tue, 29 Nov 2011 05:00:00 +0100 5456528 Identification of a second mimicry epitope from Acanthamoeba castellanii that induces CNS autoimmunity by generating cross-reactive T cells for MBP 89-101 in SJL mice http://www.medworm.com/index.php?rid=5456527&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F12%2F729%3Frss%3D1 We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139–151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89–101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108–120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89–101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108–120 develop encephalomyelitis similar to the disease induced by the cognate peptide. We demonstrate that NAD 108–120 induces T cells tha... International Immunology journals http://www.medworm.com/rss/comments.php?id=5456527 Tue, 29 Nov 2011 05:00:00 +0100 5456527 Human eosinophils express RAGE, produce RAGE ligands, exhibit PKC-delta phosphorylation and enhanced viability in response to the RAGE ligand, S100B http://www.medworm.com/index.php?rid=5456526&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F12%2F713%3Frss%3D1 This study tested the hypothesis that human eosinophils produce ligands for the receptor for advanced glycation end-products (RAGE), express RAGE and exhibit RAGE-mediated responses. In examining our microarray data, we identified the presence of RAGE and RAGE ligand (S100A4, S100A6, S100A8, S100A9, S100A11, S100P, HMGB1) transcripts. Expression of eosinophil RAGE mRNA was also compared with a known positive control and further assessed via bioinformatics and sequence analysis of RAGE cDNA. Positive and negative controls were used to identify RAGE, S100A8 and S100A9 protein in human primary eosinophils. Immunoblot assessment of eosinophils treated with cytokines (IL-5 or granulocyte macrophage colony-stimulating factor) indicated an up-regulation of S100A8 and S100A9 production, whereas co... International Immunology journals http://www.medworm.com/rss/comments.php?id=5456526 Tue, 29 Nov 2011 05:00:00 +0100 5456526 In this issue http://www.medworm.com/index.php?rid=5456525&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F12%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5456525 Tue, 29 Nov 2011 05:00:00 +0100 5456525 IL-1{beta} and TNF{alpha}-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis http://www.medworm.com/index.php?rid=5358530&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F11%2F701%3Frss%3D1 Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes irreversible joint damage and significant disability. However, the fundamental mechanisms underlying how inflammation and joint destruction in RA develop and are sustained chronically remain largely unknown. Here, we show that signal transducer and activator of transcription 3 (STAT3) is the key mediator of both chronic inflammation and joint destruction in RA. We found that inflammatory cytokines highly expressed in RA patients, such as IL-1β, tumor necrosis factor alpha and IL-6, activated STAT3 either directly or indirectly and in turn induced expression of IL-6 family cytokines, further activating STAT3 in murine osteoblastic and fibroblastic cells. STAT3 activation also induced expression of receptor activato... International Immunology journals http://www.medworm.com/rss/comments.php?id=5358530 Fri, 28 Oct 2011 04:00:00 +0100 5358530 GSK3-mediated instability of tubulin polymers is responsible for the failure of immature CD4+CD8+ thymocytes to polarize their MTOC in response to TCR stimulation http://www.medworm.com/index.php?rid=5358529&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F11%2F693%3Frss%3D1 Although mature T cells divide and differentiate when they receive strong TCR stimulation, most immature CD4+CD8+ thymocytes die. The molecular basis for this marked difference in response is not known. Observations that TCR-stimulated CD4+CD8+ thymocytes fail to polarize their microtubule-organizing center (MTOC), one of the first events that occurs upon antigen activation of mature T cells, suggests that TCR signaling routes in immature and mature T cells diverge early and upstream of MTOC polarization. To better understand the source of the divergence, we examined the molecular basis for the difference in TCR-mediated MTOC polarization. We show that unstable microtubules are a feature of immature murine CD4+CD8+ thymocytes, which also exhibit higher levels of glycogen synthase kinase 3 ... International Immunology journals http://www.medworm.com/rss/comments.php?id=5358529 Fri, 28 Oct 2011 04:00:00 +0100 5358529 IL-32 expression in the airway epithelial cells of patients with Mycobacterium avium complex lung disease http://www.medworm.com/index.php?rid=5358528&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F11%2F679%3Frss%3D1 Lung disease due to Mycobacterium avium complex (MAC) organisms is increasing. A greater understanding of the host immune response to MAC organisms will provide a foundation to develop novel therapies for these recalcitrant infections. IL-32 is a newly described pro-inflammatory cytokine that enhances host immunity against various microbial pathogens. Cytokines that induce IL-32 such as interferon-gamma, IL-18, IL-12 and tumor necrosis factor-alpha are of considerable importance to mycobacterial immunity. We performed immunohistochemistry and morphometric analysis to quantify IL-32 expression in the lungs of 11 patients with MAC lung disease and 10 controls with normal lung tissues. After normalizing for basement membrane length, there was a profound increase in IL-32 expression in the air... International Immunology journals http://www.medworm.com/rss/comments.php?id=5358528 Fri, 28 Oct 2011 04:00:00 +0100 5358528 Peripheral Th1/Th2/Th17/regulatory T-cell balance in asthmatic pregnancy http://www.medworm.com/index.php?rid=5358527&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F11%2F669%3Frss%3D1 Asthma is a common chronic disease that may complicate pregnancy and a risk factor for complications; however, immunological mechanisms of the bilateral interactions between asthma and pregnancy are not fully understood. Healthy gestation is characterized by a sensitive balance of Th1/Th2/Th17/regulatory T (Treg) cells that may be altered in asthmatic pregnancy. The aim of this study was to describe the prevalence of these cell subsets in asthmatic compared with healthy pregnancy. The prevalence of Th1, Th2, Th17 and Treg lymphocytes was identified by cell surface and intracellular marker staining in blood samples of 24 healthy non-pregnant (HNP), 23 healthy pregnant (HP), 15 asthmatic non-pregnant (ANP) and 15 asthmatic pregnant (AP) women using flow cytometry. The Th1/Th2 cell ratio was ... International Immunology journals http://www.medworm.com/rss/comments.php?id=5358527 Fri, 28 Oct 2011 04:00:00 +0100 5358527 Transcriptional control of T-cell development http://www.medworm.com/index.php?rid=5358526&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F11%2F661%3Frss%3D1 T lymphocytes, which are central players in orchestrating immune responses, consist of several subtypes with distinct functions. The thymus is an organ where hematopoietic progenitors undergo sequential developmental processes to give rise to this variety of T-cell subsets with diverse antigen specificity. In the periphery, naive T cells further differentiate into effector cells upon encountering antigens. There are several developmental checkpoints during T-cell development, where regulation by a combination of transcription factors imprints specific functional properties on precursors. The transcription factors E2A, GATA-binding protein 3 (Gata3) and RUNT-related transcription factor (Runx) are involved at various stages in the differentiation of double-negative thymocytes and in β-... International Immunology journals http://www.medworm.com/rss/comments.php?id=5358526 Fri, 28 Oct 2011 04:00:00 +0100 5358526 In this issue http://www.medworm.com/index.php?rid=5358525&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F11%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5358525 Fri, 28 Oct 2011 04:00:00 +0100 5358525 MCL1 increases primitive thymocyte viability in female mice and promotes thymic expansion into adulthood http://www.medworm.com/index.php?rid=5272845&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F10%2F647%3Frss%3D1 Increasing the pool of cells at early T-cell developmental stages enhances thymopoiesis and is especially beneficial when T-cell production is compromised by radiation or aging. Within the immature double-negative (DN; CD4–CD8–) thymocyte subpopulation, the DN1 subset contains the most primitive cells including the rare early T-cell progenitors (ETPs). In the present study, a human MCL1 transgene, under the control of its endogenous promoter, resulted in enlargement of an undistorted thymus in C57/BL6 mice. Enlargement occurred in females but not males, being seen at 1 month of age and maintained during progression into adulthood as the thymus underwent involution. The small DN1 subset was expanded disproportionally (ETPs increasing from ~0.016 to 0.03% of thymocytes), while mo... International Immunology journals http://www.medworm.com/rss/comments.php?id=5272845 Wed, 28 Sep 2011 04:00:00 +0100 5272845 Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages http://www.medworm.com/index.php?rid=5272844&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F10%2F637%3Frss%3D1 Macrophages play a pivotal role in innate immune responses to pathogens via toll-like receptors. We previously demonstrated that aryl hydrocarbon receptor (Ahr) in combination with signal transducer and activator of transcription 1 (Stat1) negatively regulates pro-inflammatory cytokine production by inhibiting nuclear factor-B activation in macrophages after LPS stimulation. Here, we show that Ahr also negatively regulates production of the pro-inflammatory cytokine IL-6 by suppressing histamine production in macrophages stimulated by LPS. We found that Ahr–Sp1 complex, independent of Stat1, represses histidine decarboxylase expression by inhibiting LPS-induced Sp1 phosphorylation on Ser residues in macrophages; this leads to suppression of histamine production. Moreover, we found th... International Immunology journals http://www.medworm.com/rss/comments.php?id=5272844 Wed, 28 Sep 2011 04:00:00 +0100 5272844 Effects of BCL-2 over-expression on B cells in transgenic rats and rat hybridomas http://www.medworm.com/index.php?rid=5272843&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F10%2F625%3Frss%3D1 The rat is an important biomedical experimental model that benefited from the recent development of new transgenic and knockout techniques. With the goal to optimize rat mAb production and to analyze the impact of Bcl-2 on B-cell development, we generated bcl-2 transgenic rats. Transgenic rats showed Bcl-2 over-expression in B cells, increased B cell numbers in lymphoid organs, elevated production of immunoglobulins (Igs) and prolonged B-cell survival in vitro. Transgenic rats remained healthy, reproduced normally and did not develop autoimmunity. Fusions with bcl-2 transgenic splenocytes did not result in increased hybridoma generation. A comparison of on- and off-rates of 39 mAbs generated with bcl-2 transgenic and wild-type animals revealed no significant differences. Over-expression of... International Immunology journals http://www.medworm.com/rss/comments.php?id=5272843 Wed, 28 Sep 2011 04:00:00 +0100 5272843 An autoimmunized mouse model recapitulates key features in the pathogenesis of Sjogren's syndrome http://www.medworm.com/index.php?rid=5272842&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F10%2F613%3Frss%3D1 The pathogenesis of Sjögren’s syndrome (SS) is poorly understood. To evaluate an autoimmunization-induced experimental SS model, we firstly observed the phenotype of lymphocyte infiltration in the enlarged submandibular gland (SG). Furthermore, significant activation of caspase-3 and a high ratio of Bax-to-Bcl-2 were detected, indicating the inflammatory apoptosis associated with developmental foci. Meanwhile, the dysregulated cytokines, such as tumor necrosis factor α, IL-1β and IL-6 mRNA expression, were found to be over-expressed. A progressive decrease of aquaporin 5 and its subcellular translocation from apical to basal membrane in SG was found to be associated with the abnormally expressed M3 muscarinic acetylcholine receptor. This pattern was found to be simila... International Immunology journals http://www.medworm.com/rss/comments.php?id=5272842 Wed, 28 Sep 2011 04:00:00 +0100 5272842 Antibodies to HIV integrase catalyze site-specific degradation of their antigen http://www.medworm.com/index.php?rid=5272841&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F10%2F601%3Frss%3D1 HIV-1 integrase (IN) catalyzes integration of a DNA copy of the viral genome into the host genome. In contrast to canonical proteases (trypsin, chymotrypsin and proteinase K), IgGs and IgMs isolated from HIV-infected patients by affinity chromatography on immobilized IN specifically hydrolyzed only IN but not many other tested intact globular proteins. The sites of IN cleavage determined by MALDI mass spectrometry were localized mainly within seven known immunodominant regions of IN. Thin layer chromatography analysis has shown that the abzymes (Abzs) could also cleave 17 to 22-mer oligopeptides (OPs) corresponding to the immunodominant regions of IN sequence with a much higher rate than non-specific long peptides or three- and tetrapeptides of various sequence. Therefore, a prolonged incu... International Immunology journals http://www.medworm.com/rss/comments.php?id=5272841 Wed, 28 Sep 2011 04:00:00 +0100 5272841 RhoB deficiency in thymic medullary epithelium leads to early thymic atrophy http://www.medworm.com/index.php?rid=5272840&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F10%2F593%3Frss%3D1 RhoB, a member of the Rho subfamily of small GTPases, mediates diverse cellular functions, including cytoskeletal organization, cell transformation and vesicle trafficking. The thymus undergoes progressive decline in its structure and function after puberty. We found that RhoB was expressed in thymic medullary epithelium. To investigate a role of RhoB in the regulation of thymic epithelial organization or thymocyte development, we analyzed the thymi of RhoB-deficient mice. RhoB-deficient mice were found to display earlier thymic atrophy. RhoB deficiency showed significant reductions in thymus weight and cellularity, beginning as early as 5 weeks of age. The enhanced expression of TGF-β receptor type II (TGFβRII) in thymic medullary epithelium was observed in RhoB-null mice. In ad... International Immunology journals http://www.medworm.com/rss/comments.php?id=5272840 Wed, 28 Sep 2011 04:00:00 +0100 5272840 In this issue http://www.medworm.com/index.php?rid=5272839&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F10%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5272839 Wed, 28 Sep 2011 04:00:00 +0100 5272839 Aurintricarboxylic acid promotes the conversion of naive CD4+CD25- T cells into Foxp3-expressing regulatory T cells http://www.medworm.com/index.php?rid=5142813&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2F583%3Frss%3D1 Naive peripheral CD4+CD25– T cells can be converted into Foxp3-expressing regulatory T cells under appropriate stimulation conditions. Considering that continuous exposure to antigens is one of the prerequisites for the differentiation and maintenance of Treg cells, we investigated whether preventing activation-induced cell death while providing continuous TCR stimulation could promote the expression of Foxp3 in murine naive CD4+ T cells. Among the several anti-apoptotic agents tested, aurintricarboxylic acid (ATA) was found to induce the in vitro conversion of naive CD4+ T cells into Foxp3+ Treg cells with suppressive activity. Neutralizing studies with an antibody against transforming growth factor (TGF)-β revealed that ATA requires the presence of TGF-β to induce Foxp3 e... International Immunology journals http://www.medworm.com/rss/comments.php?id=5142813 Tue, 16 Aug 2011 23:00:00 +0100 5142813 Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice http://www.medworm.com/index.php?rid=5142812&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2F575%3Frss%3D1 Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive swelling and erythema by arthritogenic antibody injection, whereas Tyk2-deficient mice did not show any signs of arthritis. Indeed, neither the infiltration of inflammatory cells nor the fibrillation of articular cartilages was observed in Tyk2-deficient mice. Tyk2 deficiency also reduced the production of Th1/Th17-related cytokines, the other proinflammatory cytokines and matrix metalloproteases, which are induced in the CAIA paw. Our results demonstrate a critical contributio... International Immunology journals http://www.medworm.com/rss/comments.php?id=5142812 Tue, 16 Aug 2011 23:00:00 +0100 5142812 Increased T-cell immunity against aquaporin-4 and proteolipid protein in neuromyelitis optica http://www.medworm.com/index.php?rid=5142811&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2F565%3Frss%3D1 In neuromyelitis optica (NMO), B-cell autoimmunity to aquaporin-4 (AQP4) has been shown to be essential. However, the role of T cells remains ambiguous. Here, we first showed an increase in CD69+ activated T cells in PBMCs during NMO relapses. Next, T-cell responses to AQP4 and myelin peptides were studied in 12 NM0 patients, 10 multiple sclerosis (MS) patients and 10 healthy subjects (HS). Four hours after adding 1 of 28 overlapping AQP4 peptides, a mixture of AQP4 peptides (AQP4-M) or one of six distinct myelin peptides to 2-day cultured PBMC, CD69 expression on CD4+ T cells was examined. Data were analyzed by paired t-test, frequency of samples with 3-fold increase of CD69 on CD4+ cells (fSI3) and mean stimulation index (mSI). The T-cell response to AQP4-M was significantly increased in... International Immunology journals http://www.medworm.com/rss/comments.php?id=5142811 Tue, 16 Aug 2011 23:00:00 +0100 5142811 The pre-TCR signal induces transcriptional silencing of the TCR{gamma} locus by reducing the recruitment of STAT5 and Runx to transcriptional enhancers http://www.medworm.com/index.php?rid=5142810&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2F553%3Frss%3D1 The mouse TCR locus is positively regulated by the transcription factors STAT5 and Runx. While the locus undergoes frequent rearrangements in T lymphocytes, TCR transcription is repressed in αβ T cells. This phenomenon, known as TCR silencing, depends on pre-TCR-induced thymocyte proliferation. The molecular basis for TCR silencing, however, is largely unknown. Here, we show that pre-TCR signaling reduces transcription and histone acetylation of the TCR locus irrespective of V-J rearrangements. We also demonstrate that Runx is recruited to E and HsA enhancer elements of the TCR locus, primarily at the CD4–CD8– double-negative stage and that Runx binding to these elements decreases at later stages of thymocyte development. Importantly, anti-CD3 antibody treatment decr... International Immunology journals http://www.medworm.com/rss/comments.php?id=5142810 Tue, 16 Aug 2011 23:00:00 +0100 5142810 Excessive amounts of mu heavy chain block B-cell development http://www.medworm.com/index.php?rid=5142809&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2F545%3Frss%3D1 Antigen-independent B-cell development occurs in several stages that depend on the expression of Ig heavy and light chain. We identified a line of mice that lacked mature B cells in the spleen. This mouse line carried approximately 11 copies of a transgene of the murine heavy chain constant region locus, and B-lineage cells expressed excessive amounts of the intracellular µ heavy chain. B-cell development failed in the bone marrow at the pro/pre B-cell transition, and examination of other lines with various copy numbers of the same transgene suggested that deficiencies in B-cell development increased with increased transgene copy number. Expression of a transgenic (Tg) light chain along with the Tg µ heavy chain led to minimal rescue of B-cell development in the bone marrow and... International Immunology journals http://www.medworm.com/rss/comments.php?id=5142809 Tue, 16 Aug 2011 23:00:00 +0100 5142809 Corticosteroids shift the Toll-like receptor response pattern of primary-isolated murine liver cells from an inflammatory to an anti-inflammatory state http://www.medworm.com/index.php?rid=5142808&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2F537%3Frss%3D1 Conclusions: TLR signaling is modulated by corticosteroids in a cell type-specific fashion resulting in down-regulation of TLR expression, suppression of pro-inflammatory and up-regulation of anti-inflammatory cytokines. This represents an as yet unknown mechanism of action for corticosteroids that may at least in part explain their therapeutic effects in inflammatory liver diseases. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5142808 Tue, 16 Aug 2011 23:00:00 +0100 5142808 Mucosal-associated invariant T cells regulate Th1 response in multiple sclerosis http://www.medworm.com/index.php?rid=5142807&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2F529%3Frss%3D1 Mucosal-associated invariant T (MAIT) cells are innate T cells expressing an invariant Vα7.2-Jα33 T-cell antigen receptor α chain and are enriched in mucosal-associated lymphoid tissues. Although the regulatory role of MAIT cells in experimental autoimmune encephalomyelitis has been determined, their role in multiple sclerosis (MS) has not been elucidated. In the present study, the character of MAIT cells in the peripheral blood of MS patients was analyzed. Compared with healthy controls, the frequency of MAIT cells in peripheral blood was significantly reduced in MS patients in remission and even more profoundly reduced in those with relapse. The frequency of MAIT cells reflected the disease activity, as they were reduced significantly in patients with active disease com... International Immunology journals http://www.medworm.com/rss/comments.php?id=5142807 Tue, 16 Aug 2011 23:00:00 +0100 5142807 In this issue http://www.medworm.com/index.php?rid=5142806&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F9%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5142806 Tue, 16 Aug 2011 23:00:00 +0100 5142806 Converging pathways lead to overproduction of IL-17 in the absence of vitamin D signaling http://www.medworm.com/index.php?rid=5052035&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2F519%3Frss%3D1 Multiple pathways converge to result in the overexpression of Th17 cells in the absence of either vitamin D or the vitamin D receptor (VDR). CD4+ T cells from VDR knockout (KO) mice have a more activated phenotype than their wild-type (WT) counterparts and readily develop into Th17 cells under a variety of in vitro conditions. Vitamin D-deficient CD4+ T cells also overproduced IL-17 in vitro and 1,25 dihydroxyvitamin D3 inhibited the development of Th17 cells in CD4+ T-cell cultures. Conversely, the induction of inducible (i) Tregs was lower in VDR KO CD4+ T cells than WT and the VDR KO iTregs were refractory to IL-6 inhibition. Host-specific effects of the VDR were evident on in vivo development of naive T cells. Development of naive WT CD4+ T cells in the VDR KO host resulted in the over... International Immunology journals http://www.medworm.com/rss/comments.php?id=5052035 Mon, 18 Jul 2011 23:00:00 +0100 5052035 Immunochemical properties and pathological relevance of anti-{beta}2-glycoprotein I antibodies of different avidity http://www.medworm.com/index.php?rid=5052034&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2F511%3Frss%3D1 Despite available treatment, there is still significant morbidity and mortality present among patients with the autoimmune thrombophilic condition termed ‘antiphospholipid syndrome’ (Espinosa, G. and Cervera, R. 2009. Morbidity and mortality in the antiphospholipid syndrome. Curr. Opin. Pulm. Med. 15:413.). High-avidity (HAv) anti-β2-glycoprotein I (anti-β2GPI) antibodies, shown to correlate with thrombotic events in patients, could represent the much needed improved prognostic marker. By studying their effect on crystalline annexin A5 shield on phospholipid surfaces (one of proposed pathogenic mechanisms), with the use of atomic force microscopy, the pathogenic potential of HAv anti-β2GPI antibodies was confirmed. Furthermore, by using surface plasmon resonance ... International Immunology journals http://www.medworm.com/rss/comments.php?id=5052034 Mon, 18 Jul 2011 23:00:00 +0100 5052034 Intracellular TLR4/MD-2 in macrophages senses Gram-negative bacteria and induces a unique set of LPS-dependent genes http://www.medworm.com/index.php?rid=5052033&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2F503%3Frss%3D1 Toll-like receptor (TLR)4/MD-2, a sensor for LPS, delivers the MyD88-dependent signal from the cell surface, then traffics to endolysosomes and delivers the TRIF/TICAM-1-dependent signal. Both signals are thought to be dependent on cell surface TLR4/MD-2. Although TLR4/MD-2 is located also in recycling endosomes, the Golgi apparatus or the endoplasmic reticulum, little is known about a role for intracellular TLR4/MD-2 in LPS responses. We here studied intracellular LPS sensing in macrophages. PRAT4A (protein associated with TLR4 A) is a cochaperone for a general chaperone gp96 and required for cell surface expression of TLR4/MD-2. Cell surface TLR4/MD-2 was undetectable on PRAT4A–/– thioglycollate-elicited peritoneal macrophages (P-Macs) and bone marrow-derived macrophages (BM-... International Immunology journals http://www.medworm.com/rss/comments.php?id=5052033 Mon, 18 Jul 2011 23:00:00 +0100 5052033 Identification of Fyn as the binding partner for the WASP N-terminal domain in T cells http://www.medworm.com/index.php?rid=5052032&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2F493%3Frss%3D1 Wiskott–Aldrich syndrome protein (WASP) plays important roles in TCR signaling. In transgenic (Tg) mice, over-expression of the WASP N-terminal region (exons 1–5) including the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) homology 1 (EVH1) domain and anti-WASP-EVH1 single-chain variable fragment (scFv) intracellular expressed antibodies (intrabodies) impairs IL-2 production in activated T cells. However, it largely remains unknown that how this domain transduces TCR signaling. Here, we demonstrate for the first time that the WASP N-terminal domain specifically associates with the Fyn SH3 domain; the interaction was uncovered by screening a gt11 cDNA expression library obtained from the mouse T-cell line KKF. The interaction between Fyn and WASP was inhibited by over... International Immunology journals http://www.medworm.com/rss/comments.php?id=5052032 Mon, 18 Jul 2011 23:00:00 +0100 5052032 CD4+CD25+FoxP3+ regulatory T cells enhance the allogeneic activity of endothelial-specific CD8+/CD28-CTL http://www.medworm.com/index.php?rid=5052031&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2F485%3Frss%3D1 Numerous data indicate that CD4+CD25+FoxP3+ regulatory T cells (Treg cells) can attenuate alloresponses of conventional T lymphocytes against professional antigen-presenting cells and thus qualify for clinical use in various transplant settings. However, it is unknown whether Treg cells also influence T cell–endothelial cell interactions. CD8+ PBMC (CD8+ PBMC, CTL) from healthy human donors were stimulated for 7 days with an allogeneic microvascular endothelial cell line (CDC/EU. HMEC-1, an immortalized human microvascular endothelial cell line, further referred to as HMEC) and additional endothelial cell types and analysed for their lytic activity against these target cells in the presence or absence of Treg cells. Addition of Treg cells (1:1:1) to the CTL/HMEC co-cultures in the ef... International Immunology journals http://www.medworm.com/rss/comments.php?id=5052031 Mon, 18 Jul 2011 23:00:00 +0100 5052031 Characterization of human invariant natural killer T cells expressing FoxP3 http://www.medworm.com/index.php?rid=5052030&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2F473%3Frss%3D1 Recently described forkhead box protein 3 (FoxP3) transcription factor is a key molecule in CD4+ CD25hi+ T-cell characterization. Invariant NK T (iNKT) cells are also characterized as regulatory cells modulating the immune response by rapidly producing Th1 and Th2 cytokines. We aimed to analyze cellular markers important in regulatory features of human iNKT cells and to study their role in functional assays. iNKT cells were single cell sorted from peripheral mononuclear cells of healthy individuals after immunostaining of invariant TCR α-chain. We found FoxP3 expression in human iNKT clones. Randomly selected iNKT cell clones (CD4+, double negative, CD8+) expressed FoxP3 mRNA and protein at different levels upon stimulation as supported by various approaches. FoxP3 mRNA and protein e... International Immunology journals http://www.medworm.com/rss/comments.php?id=5052030 Mon, 18 Jul 2011 23:00:00 +0100 5052030 Dectin-1 and Dectin-2 in innate immunity against fungi http://www.medworm.com/index.php?rid=5052029&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2F467%3Frss%3D1 Dectin-1 and Dectin-2 are type II transmembrane proteins of the C-type lectin family with single carbohydrate recognition domains (CRDs) in their extracellular region. They are expressed mainly in dendritic cells and macrophages. Dectin-1 recognizes β-glucans with its CRD and transduces signals through its immunoreceptor tyrosine-based activation motif (ITAM)-like motif in the cytoplasmic domain, whereas Dectin-2 recognizes α-mannans and transduces its signal through association with the ITAM-containing Fc receptor chain. Upon ligand binding, spleen tyrosine kinase is recruited to the ITAM and activates the caspase recruitment domain family member 9 (CARD9)–nuclear factor-B axis, resulting in the activation of various genes including those encoding pro-inflammatory cytokin... International Immunology journals http://www.medworm.com/rss/comments.php?id=5052029 Mon, 18 Jul 2011 23:00:00 +0100 5052029 In this issue http://www.medworm.com/index.php?rid=5052028&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F8%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=5052028 Mon, 18 Jul 2011 23:00:00 +0100 5052028 RETRACTION of: Amelioration of hepatic fibrosis via beta-glucosylceramide-mediated immune modulation is associated with altered CD8 and NKT lymphocyte distribution http://www.medworm.com/index.php?rid=4969369&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F465%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4969369 Sun, 26 Jun 2011 23:00:00 +0100 4969369 Corrigendum http://www.medworm.com/index.php?rid=4969368&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F463%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4969368 Sun, 26 Jun 2011 23:00:00 +0100 4969368 Coupling presentation of MHC class I peptides to constitutive activation of antigen-presenting cells through the product of a single gene http://www.medworm.com/index.php?rid=4969367&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F453%3Frss%3D1 Priming of naive CD8 T cells by dendritic cells (DCs) entails both effective antigen presentation on MHC class I products and co-stimulatory signaling. Their optimal coupling is a major goal in the development of CTL-inducing vaccines. We recently reported that a membranal derivative of the invariant MHC-I light chain, β2-microglobulin (β2m), markedly stabilizes MHC-I molecules and can serve as a universal platform for exceptional presentation of genetically linked peptides. To test whether it is possible to equip the resulting MHC-I complexes with an inherent ability to activate antigen-presenting cells, we engrafted the intracellular Toll/IL-1 receptor domain of mouse Toll-like receptor (TLR) 4 or TLR2 onto the peptide-β2m scaffold. We evaluated the level of peptide presen... International Immunology journals http://www.medworm.com/rss/comments.php?id=4969367 Sun, 26 Jun 2011 23:00:00 +0100 4969367 Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats http://www.medworm.com/index.php?rid=4969366&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F443%3Frss%3D1 Tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of asthma, and neutralization of TNF-α is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-α antibody, infliximab, may be useful in the management of asthma. E3 rats were immunized with ovalbumin (OVA)/alum and received infliximab intra-peritoneally. Two weeks later, OVA–PBS was instilled intranasally daily for 7 days. Bronchoalveolar lavage fluids (BALFs), serum and lung homogenates were collected for analysis of cells and inflammatory mediators. Contractile responses of lobar-bronchus segments to agonists were functionally tested. Pulmonary tissues were investigated using histological examination. The results showed that the sensitized ‘m... International Immunology journals http://www.medworm.com/rss/comments.php?id=4969366 Sun, 26 Jun 2011 23:00:00 +0100 4969366 HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice http://www.medworm.com/index.php?rid=4969365&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F433%3Frss%3D1 The viral protein Nef is a key element for the progression of HIV disease. Previous in vitro studies suggested that Nef expression in T-cell lines enhanced TCR signaling pathways upon stimulation with TCR cross-linking, leading to the proposal that Nef lowers the threshold of T-cell activation, thus increasing susceptibility to viral replication in immune response. Likewise, the in vivo effects of Nef transgenic mouse models supported T-cell hyperresponse by Nef. However, the interpretation is complicated by Nef expression early in the development of T cells in these animal models. Here, we analyzed the consequence of Nef expression in ovalbumin-specific/CD4+ peripheral T cells by using a novel mouse model and demonstrate that Nef inhibits antigen-specific T-cell proliferation and multiple... International Immunology journals http://www.medworm.com/rss/comments.php?id=4969365 Sun, 26 Jun 2011 23:00:00 +0100 4969365 The 'T-cell-ness' of NK cells: unexpected similarities between NK cells and T cells http://www.medworm.com/index.php?rid=4969364&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F427%3Frss%3D1 NK cells are considered as prototypical innate immune cells. However, recent discoveries have tended to refine the dogmatic concepts of innate and adaptive immunity. In many ways, NK cells are highly related to T cells and represent the closest innate immune cell lineage to adaptive immune cell populations. Here, we review the relationships between NK cells and T cells and discuss the recently described cell-intrinsic-adaptive features of NK cells. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4969364 Sun, 26 Jun 2011 23:00:00 +0100 4969364 A trio of microRNAs that control Toll-like receptor signalling http://www.medworm.com/index.php?rid=4969363&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F421%3Frss%3D1 Toll-like receptors (TLRs) in the host recognize conserved microbial products and defend against pathogenic attack by initiating an immune response via signalling pathways that lead to an increase in immune and inflammatory gene expression. TLR signalling must be stringently regulated in order to ensure sufficient clearance of pathogens and a timely return to homeostasis after infection. MicroRNAs (miRNAs) are a newly discovered class of gene regulators which bind to the 3' untranslated region of target mRNA and direct their post-transcriptional repression. They are global regulators potentially controlling up to 30% of the human genome. Several miRNAs have been shown to be up-regulated in response to TLR ligands, and many directly target components of the TLR signalling system, revealing ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4969363 Sun, 26 Jun 2011 23:00:00 +0100 4969363 An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation http://www.medworm.com/index.php?rid=4969362&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2F415%3Frss%3D1 CD4 Th are critical for orchestrating adaptive immune responses. The expression of the transcription factor GATA3 (GATA-binding protein 3) is up-regulated or down-regulated during Th2 or Th1 cell differentiation, respectively. Furthermore, GATA3 is responsible for induction of Th2 differentiation and represses Th1 differentiation. In this review, we present an updated view on the molecular mechanisms through which GATA3 regulates Th1/Th2 differentiation. During Th2 cell differentiation, GATA3 directly binds to the Th2 cytokine gene locus at several regions and regulates expression. On the other hand, GATA3 inhibits Th1 cell differentiation by preventing up-regulation of IL-12 receptor β2 and STAT4 (signal transducer and activator of transcription 4) and neutralization of Runx3 (runt-r... International Immunology journals http://www.medworm.com/rss/comments.php?id=4969362 Sun, 26 Jun 2011 23:00:00 +0100 4969362 In this issue http://www.medworm.com/index.php?rid=4969361&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F7%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4969361 Sun, 26 Jun 2011 23:00:00 +0100 4969361 Specific expression of PAD4 and citrullinated proteins in lung cancer is not associated with anti-CCP antibody production http://www.medworm.com/index.php?rid=4872818&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F6%2F405%3Frss%3D1 In conclusion, PAD4 and citrullination may be helpful in distinguishing lung cancer from healthy tissue. Smoking, abnormal serum PAD4 and RF levels may not be sufficient for the production of ACPAs and development of autoimmunity. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4872818 Thu, 26 May 2011 23:00:00 +0100 4872818 Generation and characterization of peptide mimotopes specific for anti ErbB-2 monoclonal antibodies http://www.medworm.com/index.php?rid=4872817&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F6%2F391%3Frss%3D1 The erbb-2 gene receptor is often over-expressed in human cancer and its overexpression is accompanied by worse prognosis. Targeting erbb-2 gene with antibodies is an effective approach to curtail the progression of erbb-2 gene-expressing cancer types. Two monoclonal antibodies, L-26 and N-12, previously generated in our laboratory, have shown effective tumor inhibition in mice, especially when used in combination. Here, we describe novel peptide mimics of erbb-2 gene protein epitopes, also called mimotopes, that were selected from a constraint random 12-mer peptide phage library, specific for the antibodies L-26 and N-12. Initial sequencing analyses revealed little sequence conservation among the peptide mimotopes, and no sequence homology with the erbb-2 gene protein. However, computatio... International Immunology journals http://www.medworm.com/rss/comments.php?id=4872817 Thu, 26 May 2011 23:00:00 +0100 4872817 Recombination activation gene-2-deficient blastocyst complementation analysis reveals an essential role for nuclear factor I-A transcription factor in T-cell activation http://www.medworm.com/index.php?rid=4872816&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F6%2F385%3Frss%3D1 Nuclear factor I (NFI)-A is a member of the NFI family of transcription factors implicated in regulation of granulocyte differentiation. However, its role in the lymphoid lineage is not known. NFI-A deficiency results in perinatal lethality, thus precluding analysis of the role of NFI-A in lymphocyte development and function. Using recombination activation gene-2-deficient (RAG-2–/–) blastocysts and embryonic stem cells with homozygous NFI-A gene deletion, we show an essential role for NFI-A in T-cell activation. NFI-A–/–->RAG-2–/– chimeric mice had normal distributions of CD4–CD8– double negative, CD4+CD8+ double positive, CD4+CD8– and CD4–CD8+-single positive cells in the thymus and CD4+CD8– and CD4–CD8+ cells in ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4872816 Thu, 26 May 2011 23:00:00 +0100 4872816 The B lineage transcription factor E2A regulates apoptosis in chronic lymphocytic leukemia (CLL) cells http://www.medworm.com/index.php?rid=4872815&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F6%2F375%3Frss%3D1 Chronic lymphocytic leukemia (CLL) is a common malignancy characterized by the accumulation of B lymphocytes with an antigen-experienced activated CD19+CD5+ clonal phenotype. Clinically, ~50% of cases will behave more aggressively. Here, we investigate the role of the major B-cell transcription factor E2A, a known regulator of B-cell survival and proliferation, to CLL persistence. We show that E2A is elevated at the mRNA and protein levels relative to normal B-cell subsets. E2A silencing in primary CLL cells leads to a significant increase in spontaneous apoptosis in both CD38+ (aggressive) and CD38– (indolent) cases. Moreover, E2A knockdown synergizes with the immunomodulatory drug lenalidomide to reduce CLL viability. E2A is known to restrain the proliferation of primary B and T ly... International Immunology journals http://www.medworm.com/rss/comments.php?id=4872815 Thu, 26 May 2011 23:00:00 +0100 4872815 Antigen-independent development of Foxp3+ regulatory T cells suppressing autoantibody production in experimental pemphigus vulgaris http://www.medworm.com/index.php?rid=4872814&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F6%2F365%3Frss%3D1 In this study, we examined whether the specific antigen is involved in the development of polyclonal Tregs in pemphigus vulgaris (PV), an autoimmune blistering disease caused by anti-desmoglein 3 (Dsg3) IgG antibodies, as a model system. Adoptive transfer of splenocytes of Dsg3–/– mice immunized with recombinant mouse Dsg3 to Rag2–/– recipient mice expressing Dsg3 resulted in the stable production of anti-Dsg3 IgG and the development of PV phenotypes. We show here that Tregs control anti-Dsg3 antibody production in PV model mice: the adoptive transfer of Tregs and the depletion of endogenous Tregs suppressed and augmented, respectively, the anti-Dsg3 antibody production. To examine whether the endogenous expression of Dsg3 is involved in the generation of these PV-r... International Immunology journals http://www.medworm.com/rss/comments.php?id=4872814 Thu, 26 May 2011 23:00:00 +0100 4872814 Bacterial LPS up-regulated TLR3 expression is critical for antiviral response in human monocytes: evidence for negative regulation by CYLD http://www.medworm.com/index.php?rid=4872813&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F6%2F357%3Frss%3D1 In this study, we provide direct evidence that bacterial LPS enhances the host antiviral response by up-regulating TLR3 expression in human peripheral blood monocytes and monocytic cell lines, THP1 cells. Moreover, LPS induces TLR3 expression via a TLR4-MyD88-IRAK-TRAF6-NF-B-dependent signaling pathway. Interestingly, CYLD, an important deubiquitinase, acts as a negative regulator of TLR3 induction by LPS. Our study thus provides new insights into a novel role for bacterial infection in enhancing host antiviral response; furthermore, it identifies CYLD for the first time as a critical negative regulator of bacterial LPS-induced response. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4872813 Thu, 26 May 2011 23:00:00 +0100 4872813 In this issue http://www.medworm.com/index.php?rid=4872812&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F6%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4872812 Thu, 26 May 2011 23:00:00 +0100 4872812 Affinity maturation of B cells involves not only a few but a whole spectrum of relevant mutations http://www.medworm.com/index.php?rid=4754454&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F5%2F345%3Frss%3D1 Affinity maturation of B lymphocytes within germinal centers involves both diversification of their B-cell receptors (BCRs) by somatic hypermutation (SHM) and a crucial receptor-mediated selection step. However, in contrast to recent advances in revealing the molecular mechanism of SHM, the fundamentals of the selection process are still poorly understood, i.e. it is often not clear how and how many mutations contribute to improving a BCR during the response against a given antigen. A general drawback in assessing the mutations relevant to the selection process is the difficult task of rating the relative contributions of selection and intrinsic biases to the experimentally observed mutation patterns of BCRs. The approach proposed here is premised on statistical comparison of the frequency... International Immunology journals http://www.medworm.com/rss/comments.php?id=4754454 Mon, 25 Apr 2011 23:00:00 +0100 4754454 Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice http://www.medworm.com/index.php?rid=4754453&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F5%2F335%3Frss%3D1 In this study, we investigated the role of BTLA in the pathogenesis of autoimmune diseases in MRL-lpr mice. We found that BTLA-deficient (BTLA–/–) MRL-lpr/lpr mice developed severe lymphocytic infiltration in salivary glands, lungs, pancreas, kidneys and joints as compared with BTLA-sufficient (BTLA+/+) MRL-lpr/lpr mice. In addition, although AIH-like disease was not found in BTLA+/+ MRL-lpr/lpr mice, AIH-like disease was exacerbated in BTLA–/– MRL-lpr/lpr mice as compared with that in BTLA–/– 129SvEv mice. These results suggest that BTLA plays a protective role in autoimmune diseases in MRL-lpr mice and that AIH-like disease develops in BTLA–/– mice even in the absence of Fas-dependent signaling. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4754453 Mon, 25 Apr 2011 23:00:00 +0100 4754453 Calcineurin subunit B activates dendritic cells and acts as a cancer vaccine adjuvant http://www.medworm.com/index.php?rid=4754452&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F5%2F327%3Frss%3D1 Safe and potent adjuvants are required to establish effective vaccines. In the present work, we show that calcineurin subunit B promotes the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-12p70 (IL-12 p70), IL-6 and the chemokine IL-8. It also up-regulates transcript levels of chemokines in bone marrow-derived dendritic cells. In an animal model, C57BL/6 mice were divided into four groups, immunized with ovalbumin (OVA), OVA mixed with calcineurin subunit B (CnB), CnB and PBS, respectively. The splenocytes from mice immunized with OVA in combination with CnB produced higher levels of IFN- and CTL when in vitro stimulated with OVA protein. Subcutaneous (s.c.) immunization of C57BL/6 mice with OVA plus CnB conferred greater protection against tumo... International Immunology journals http://www.medworm.com/rss/comments.php?id=4754452 Mon, 25 Apr 2011 23:00:00 +0100 4754452 Mouse neutrophils are professional antigen-presenting cells programmed to instruct Th1 and Th17 T-cell differentiation http://www.medworm.com/index.php?rid=4754451&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F5%2F317%3Frss%3D1 Neutrophils play a major role in the innate immune system and are normally considered to be short-lived effector cells that exert anti-microbial activity and sometimes immunopathology. Here, we show that these cells possess an additional function as professional antigen-presenting cells capable of priming a Th1- and Th17-acquired immune response. Using flow cytometry, fluorescence microscopy and western blotting, we show that mouse neutrophils express MHC class II and co-stimulatory molecules CD80 and CD86 after T-cell co-incubation. Neutrophils pulsed with ovalbumin (OVA) process and present peptide antigen to OVA-specific T cells in an MHC class II-dependent manner. Importantly, we demonstrate that neutrophils can prime antigen-specific Th1 and Th17 immune responses even without the addi... International Immunology journals http://www.medworm.com/rss/comments.php?id=4754451 Mon, 25 Apr 2011 23:00:00 +0100 4754451 Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation http://www.medworm.com/index.php?rid=4754450&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F5%2F307%3Frss%3D1 In this study, we demonstrate that IL-33 is important for allergic lung inflammation. Intra-nasal administration of IL-33 triggered an immediate allergic response in the airways, and more importantly, we show that endogenous IL-33 contributes to airway inflammation and peripheral antigen-specific responses in ovalbumin-induced acute allergic lung inflammation using IL-33-deficient mice. Our results suggest that IL-33 is sufficient and required for severe allergic inflammation in the lung and support the concept of IL-33 as a therapeutic target in allergic lung inflammation. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4754450 Mon, 25 Apr 2011 23:00:00 +0100 4754450 Regulation of TCR V{gamma}2 gene rearrangement by the helix-loop-helix protein, E2A http://www.medworm.com/index.php?rid=4754449&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F5%2F297%3Frss%3D1 In this study, we demonstrated that V2 rearrangement in the adult thymus was substantially reduced in mice deficient for the basic helix-loop-helix protein, E2A. The decreased rearrangement is likely caused by the reduced accessibility of V2 chromatin, since germ line transcription and histone acetylation of the V2 gene were reduced in an E2A dosage-dependent manner. We further showed that E2A bound around the V2 gene in vivo and we identified two canonical E-box sites downstream of V2, to which E2A can bind in vitro. Furthermore, these two E-box sites had the ability to activate transcription upon E2A over-expression. These data suggest that E2A directly binds to and increases accessibility of V2 chromatin, thereby facilitating V2 rearrangement in the adult thymus. (Source: International ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4754449 Mon, 25 Apr 2011 23:00:00 +0100 4754449 In this issue http://www.medworm.com/index.php?rid=4754448&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F5%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4754448 Mon, 25 Apr 2011 23:00:00 +0100 4754448 PML is a key component for the differentiation of myeloid progenitor cells to macrophages http://www.medworm.com/index.php?rid=4653907&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F4%2F287%3Frss%3D1 IFN regulatory factor-8 (IRF-8, previously known as ICSBP) is a key transcription factor driving the differentiation of granulocyte\monocyte progenitor (GMP) cells toward monocyte\macrophage lineage. The promyelocytic leukemia (PML) gene is an immediate target gene regulated by IRF-8 in response to IFN- activation. PML is a multifunctional protein that has many isoforms serving as the scaffold components for nuclear bodies (NBs) engaged in numerous proteins interactions. The role of PML in the retinoic acid pathway that drives GMPs to granulopoiesis is documented in the literature. Here, we show that PML is also involved in monopoiesis by mediating some of the IRF-8 activities during the differentiation of murine-derived bone marrow macrophages (BMMs). PML silencing resulted in altered exp... International Immunology journals http://www.medworm.com/rss/comments.php?id=4653907 Mon, 28 Mar 2011 23:00:00 +0100 4653907 Characterization of memory B cells responsible for affinity maturation of anti- (4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies http://www.medworm.com/index.php?rid=4653906&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F4%2F271%3Frss%3D1 We searched for memory B cells responsible for high-affinity anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibody production by C57BL/6 mice immunized with NP-chicken -globulin (CGG), using flow cytometry. We first prepared transfectants expressing B-cell antigen receptor (BCR) of known affinity as a memory B-cell model as well as NP-allophycocyanin (APC) of different NP valences, NPlo, NPmed and NPhi. We then used the latter as probes capable of distinguishing BCR affinities: NPlo-APC bound to BCRs with an affinity higher than 3.4 x 106 M–1, while NPmed-APC bound to those with a higher than germline affinity. B cells capable of binding to NPlo-APC appeared in spleens on day 14 post-immunization, and harbored Tyr95 (Tyr95 type) as well as a mutation from Trp33 to Leu. B cells with BCRs... International Immunology journals http://www.medworm.com/rss/comments.php?id=4653906 Mon, 28 Mar 2011 23:00:00 +0100 4653906 CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch http://www.medworm.com/index.php?rid=4653905&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F4%2F261%3Frss%3D1 M cells are responsible for uptake of mucosal antigens in Peyer's patches (PPs). Differentiation of M cells is thought to be induced by interactions between follicle-associated epithelium and PP cells; however, it remains elusive what types of immune cells function as M-cell inducers. Here, we attempted to identify the cells that serve as an M-cell inducer in PP. We found that a unique B-cell subset characterized by CCR6hiCD11cint resided in the subepithelial dome (SED) in mouse PP. CCR6hiCD11cint B cells showed chemotactic migration in response to CCL20. Furthermore, this unique B-cell subset substantially decreased in PP of CCR6-deficient mice, indicating that the SED localization of CCR6hiCD11cint B cells is most likely regulated by the CCL20–CCR6 system. Concomitantly, CCR6 defic... International Immunology journals http://www.medworm.com/rss/comments.php?id=4653905 Mon, 28 Mar 2011 23:00:00 +0100 4653905 Reduction of CD1d expression in vivo minimally affects NKT-enhanced antibody production but boosts B-cell memory http://www.medworm.com/index.php?rid=4653904&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F4%2F251%3Frss%3D1 The CD1d-binding glycolipid α-galactosylceramide exerts potent adjuvant effects on T-dependent humoral immunity. The mechanism is driven by cognate interaction between CD1d-expressing B cells and TCR-expressing type I CD1d-restricted NKT cells. Thus, far positive effects of alpha-galactosylceramide have been observed on initial and sustained antibody titers as well as B-cell memory. Following vaccination, each of these features is desirable, but good B-cell memory is of paramount importance for long-lived immunity. We therefore tested the hypothesis that CD1d expression in vivo differentially affects initial antibody titers versus B-cell memory responses. CD1d+/+ and CD1d+/– mice were generated and immunized with antigen plus CD1d ligand before analysis of cytokine expression, ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4653904 Mon, 28 Mar 2011 23:00:00 +0100 4653904 ICOS ligand expression is essential for allergic airway hyperresponsiveness http://www.medworm.com/index.php?rid=4653903&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F4%2F239%3Frss%3D1 Inducible co-stimulator ligand (ICOSL) is a rather newly defined co-stimulatory molecule, which, through interaction with ICOS expressed on T cells, plays an important role in T-cell activation, differentiation and function. Th2-type immune responses are critical for the development and maintenance of allergic responses including asthma. Using knockout (KO) mice, we have assessed the role of ICOSL in allergic airway inflammation and responsiveness using a standard mouse asthma model induced by ovalbumin (OVA) sensitization and challenge. Our data show that OVA-treated ICOSL KO mice exhibit significantly less lung eosinophilic infiltration, histopathology, mucus production and virtually no airway hyperresponsiveness in contrast to wild-type (Wt) counterparts. Serum antibody analysis showed ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4653903 Mon, 28 Mar 2011 23:00:00 +0100 4653903 Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells http://www.medworm.com/index.php?rid=4653902&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F4%2F223%3Frss%3D1 Extracellular heat shock protein can deliver associated antigens into the MHC class I presentation pathway of antigen-presenting cells, a process called cross-presentation, thus inducing antigen-specific CD8+ T-cell responses; however, the precise mechanism for intracellular antigen translocation and the processing pathway has not been fully elucidated. Here we demonstrate that cross-presentation of extracellular Hsp90–ovalbumin (OVA) protein complexes to specific CD8+ T cells involves both classical proteasome–transporter-associated antigen processing (TAP)-dependent and TAP-independent–endosomal pathways. Using confocal microscopy, we found that the internalized extracellular Hsp90 and OVA co-localized with cytosolic proteasomes. When anti-Hsp90 mAb was introduced to de... International Immunology journals http://www.medworm.com/rss/comments.php?id=4653902 Mon, 28 Mar 2011 23:00:00 +0100 4653902 In this issue http://www.medworm.com/index.php?rid=4653901&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F4%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4653901 Mon, 28 Mar 2011 23:00:00 +0100 4653901 Ligation of CD46 to CD40 inhibits CD40 signaling in B cells http://www.medworm.com/index.php?rid=4571369&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2F215%3Frss%3D1 CD40 induces B cells to switch to IgE in the presence of IL-4 and up-regulates their expression of the low-affinity receptor for IgE, CD23, which promotes the immune response to allergen complexed with IgE antibody. CD40 binds to CD40L and to the C4b-binding protein (C4BP) using distinct sites. CD46 is a receptor for the product of activated complement C4b. Some microbial antigens bind both C4BP and CD46, potentially bridging CD40 to CD46. In addition, immune complexes containing both C4b and C4BP may cross-link CD40 to CD46. We demonstrate that cross-linking CD46 to CD40 on B cells inhibits CD40-mediated up-regulation of surface CD23 expression and induction of IL-4-dependent IgE isotype switching. This was associated with inhibition of induction of C germ line transcripts and of activati... International Immunology journals http://www.medworm.com/rss/comments.php?id=4571369 Thu, 10 Mar 2011 00:00:00 +0100 4571369 Optimal oligonucleotide sequences for TLR9 inhibitory activity in human cells: lack of correlation with TLR9 binding http://www.medworm.com/index.php?rid=4571368&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2F203%3Frss%3D1 Toll-like receptor (TLR)9 performs our innate response to bacterial DNA, warning us of the presence of infection. Inhibitory oligodeoxyribonucleotides (INH-ODN) have been developed that selectively block activation of mouse TLR9. Their inhibitory motif consisting of CCx(not-C)(not-C)xxGGG (x = any base) also reduces anti-DNA antibodies in lupus mice. The current study demonstrates that this motif also provides the sequences required to block TLR9 in human B cells and human embryonic kidney (HEK) cells transfected with human TLR9. However, extending the sequence by four to five bases at the 5' end enhanced activity and this enhancement was greater when a phosphorothioate (pS) backbone replaced the native phosphodiester (pO) backbone. A series of pO-backbone INH-ODN representing a 500-fold r... International Immunology journals http://www.medworm.com/rss/comments.php?id=4571368 Thu, 10 Mar 2011 00:00:00 +0100 4571368 Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations http://www.medworm.com/index.php?rid=4571367&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2F195%3Frss%3D1 Suppressor of cytokine signaling (SOCS) 3 is a major negative feedback regulator of signal transducer and activator of transcription 3-activating cytokines. Studies using T-cell-specific SOCS3-deficient mice indicate that the absence of SOCS3 in T cells results in exacerbation of disease progression after infection by Leishmania major due to skewing of the Th3 cell phenotype accompanied by hyper-production of IL-10 and transforming growth factor β (TGF-β). Here we show that transgenic mice over-expressing the SOCS3 gene in T cells (Lck-SOCS3 Tg mice) are also susceptible to infection by L. major. Forced expression of SOCS3 in T cells did not affect the production of the anti-inflammatory cytokines IL-10 and TGF-β or that of the protective Th1 type cytokine IFN-, which is req... International Immunology journals http://www.medworm.com/rss/comments.php?id=4571367 Thu, 10 Mar 2011 00:00:00 +0100 4571367 Human anti-microbial cathelicidin peptide LL-37 suppresses the LPS-induced apoptosis of endothelial cells http://www.medworm.com/index.php?rid=4571366&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2F185%3Frss%3D1 In this study, to further elucidate the action of LL-37 on severe sepsis/endotoxin shock, we investigated the effects of LL-37 on the LPS-induced endothelial cell apoptosis in vitro and in vivo using lung-derived normal human microvascular blood vessel endothelial cells (HMVEC-LBls) and D-galactosamine hydrochloride (D-GalN)-sensitized murine endotoxin shock model. LL-37 suppressed the LPS-induced apoptosis of HMVEC-LBls. In addition, LL-37 inhibited the binding of LPS possibly to the LPS receptors (CD14 and toll-like receptor 4) expressed on the cells. Thus, LL-37 can suppress the LPS-induced apoptosis of HMVEC-LBls via the inhibition of LPS binding to the cells. Furthermore, LL-37 drastically suppressed the apoptosis of hepatic endothelial cells as well as hepatocytes in the liver of mur... International Immunology journals http://www.medworm.com/rss/comments.php?id=4571366 Thu, 10 Mar 2011 00:00:00 +0100 4571366 Anti-arthritic effect of E3 ubiquitin ligase, c-MIR, expression in the joints http://www.medworm.com/index.php?rid=4571365&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2F177%3Frss%3D1 Cellular modulator of immune recognition (c-MIR) is an E3 ubiquitin ligase that ubiquitinates MHC class II and CD86 for their endocytosis and subsequent lysosomal degradation. In accordance with their importance in antigen presentation, systemic c-MIR over-expression downmodulates adaptive immune responses. Rheumatoid arthritis (RA) is a chronic synovitis driven by autoimmunity in the joints. Since antigen-presenting cells, such as macrophages, dendritic cells (DCs) and rheumatoid factor-positive B cells are abundant in the rheumatoid synovial tissues, autoantigens released by tissue damage should be presented locally, leading to amplification of systemic arthritogenic immune responses. Assuming that inhibition of the antigen presentation in the synovial tissues should suppress systemic ar... International Immunology journals http://www.medworm.com/rss/comments.php?id=4571365 Thu, 10 Mar 2011 00:00:00 +0100 4571365 SOCS1 regulates type I/type II NKT cell balance by regulating IFN{gamma} signaling http://www.medworm.com/index.php?rid=4571364&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2F165%3Frss%3D1 Suppressor of cytokine signaling-1 (SOCS1) has been shown to be an essential negative regulator of cytokine responses, including those of IFN, IL-2, IL-4 and IL-7. SOCS1 deficiency resulted in hyperactivation not only of T cells in general but also of NKT cells specifically. Consistent with previous reports, T- and NKT-cell-specific deletion of Socs1 in mice resulted in enhanced sensitivity to ConA-induced hepatitis. Compared with wild-type (WT) NKT cells, SOCS1-deficient NKT cells produced larger quantities of IFN in response to ConA and proliferated faster in response to IL-2 and IL-15. To our surprise, however, SOCS1-deficient NKT cells did not respond to the synthetic glycolipid ligand alpha-galactosylceramide (α-GalCer), though they did respond to sulfatide. α-GalCer-CD1d-... International Immunology journals http://www.medworm.com/rss/comments.php?id=4571364 Thu, 10 Mar 2011 00:00:00 +0100 4571364 Recent advances in IL-22 biology http://www.medworm.com/index.php?rid=4571363&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2F159%3Frss%3D1 Several cell types, in particular epithelial cells, express the receptor for the cytokine IL-22 and upon its recognition produce molecules that are active both locally and systemically. Many different types of lymphocyte secrete IL-22. Th17 cells produce IL-22 although the optimal conditions for secretion of IL-17 or IL-22 by Th17 cells differ, as do the transcription factors involved. Aryl hydrocarbon receptor is required for IL-22 production by Th17, Th22 and T cells. Th22 cells produce IL-22 in response to IL-6 and tumor necrosis factor α (TNF-α), particularly in the skin, whereas T cells produce IL-22 in response to IL-23, particularly in the lung. NK cells produce IL-22 in response to IL-12 and IL-18 or IL-23. Retinoic acid-related orphan receptort-positive innate lymphoid... International Immunology journals http://www.medworm.com/rss/comments.php?id=4571363 Thu, 10 Mar 2011 00:00:00 +0100 4571363 In this issue http://www.medworm.com/index.php?rid=4571362&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F3%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4571362 Thu, 10 Mar 2011 00:00:00 +0100 4571362 Auto-antibody production and glomerulonephritis in congenic Slamf1-/- and Slamf2-/- [B6.129] but not in Slamf1-/- and Slamf2-/- [BALB/c.129] mice http://www.medworm.com/index.php?rid=4411973&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F149%3Frss%3D1 Several genes in an interval of human and mouse chromosome 1 are associated with a predisposition for systemic lupus erythematosus. Congenic mouse strains that contain a 129-derived genomic segment, which is embedded in the B6 genome, develop lupus because of epistatic interactions between the 129-derived and B6 genes, e.g. in B6.129chr1b mice. If a gene that is located on chromosome 1 is altered through homologous recombination in 129-derived embryonic stem cells (ES cells) and if the resultant knockout mouse is backcrossed with B6, interpretation of the phenotype of the mutant mouse may be affected by epistatic interactions between the 129 and B6 genomes. Here, we report that knockout mice of two adjacent chromosome 1 genes, Slamf1–/– and Slamf2–/–, which were gen... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411973 Fri, 28 Jan 2011 00:00:00 +0100 4411973 Impaired IFN-{gamma} production and proliferation of NK cells in Multiple Sclerosis http://www.medworm.com/index.php?rid=4411972&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F139%3Frss%3D1 NK cells are multicompetent lymphocytes of the innate immune system with a central role in host defense and immune regulation. Studies in experimental animal models of multiple sclerosis (MS) provided evidence for both pathologic and protective effects of NK cells. Humans harbor two functionally distinct NK-cell subsets exerting either predominantly cytotoxic (CD56dimCD16+) or immunoregulatory (CD56brightCD16–) functions. We analyzed these two subsets and their functions in the peripheral blood of untreated patients with relapsing-remitting MS compared with healthy blood donors. While ex vivo frequencies of CD56brightCD16– and CD56dimCD16+ NK cells were similar in patients and controls, we found that cytokine-driven in vitro accumulation and IFN- production of CD56brightCD16&nd... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411972 Fri, 28 Jan 2011 00:00:00 +0100 4411972 The WSX-1 pathway restrains intestinal T-cell immunity http://www.medworm.com/index.php?rid=4411971&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F129%3Frss%3D1 In this study, LPS increased Staphylococcus aureus enterotoxin A-specific T cells in the gut through induction of IL-12 family members. Mice deficient in IL-12 (p35–/–) favored Th17 differentiation in lamina propria, whereas mice lacking both IL-12 and IL-23 (p40–/–) produced significantly fewer Th17 cells. However, serum analysis revealed that IL-27p28 was much higher and sustained following LPS injection than other IL-12 family cytokines. Strikingly, WSX-1 (IL-27R) deficiency resulted in log-fold increases in lamina propria Th17 cells without affecting Th1 numbers. These results may be explained by increased expression of 4β7 on WSX-1-deficient T cells after immunization. WSX-1-deficient regulatory T cells (Tregs) were also perturbed, producing more IL-17 and... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411971 Fri, 28 Jan 2011 00:00:00 +0100 4411971 Antigen-specific splenic CD4+ and CD8+ regulatory T cells generated via the eye, suppress Experimental Autoimmune Encephalomyelitis either at the priming or at the effector phase http://www.medworm.com/index.php?rid=4411970&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F119%3Frss%3D1 The injection of antigen into the ocular anterior chamber (AC) induces the generation of splenic CD4+ and CD8+ regulatory T (Treg) cells, specific for the antigen injected into the AC. These Treg cells inhibit the induction (CD4+) and also the expression (CD8+) of a delayed-type hypersensitivity response. The ability of AC-induced self-antigen-specific Treg cells in modulating autoimmunity is not well defined. Here we show that an injection of encephalitogenic myelin oligodendrocyte glycoprotein (MOG35–55) peptide into the anterior chamber of the eye (AC-MOG), before the induction of or during established experimental autoimmune encephalomyelitis (EAE) induced by MOG35–55, suppresses the induction or progression of EAE, respectively. CD4+ or CD8+ splenic Treg cells induced by a... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411970 Fri, 28 Jan 2011 00:00:00 +0100 4411970 NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption http://www.medworm.com/index.php?rid=4411969&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F109%3Frss%3D1 Long-term side effects may represent a relevant burden of antiretroviral treatment (ART) in HIV-infected patients with good CD4 immune reconstitution over extended time spans. CD4-guided treatment interruption (TI) has been evaluated to address this point and may result in a wide spectrum of time off ART in different patient cohorts. We studied whether differences in innate immune responses, in particular NK cells, are associated to patterns of longer (LoTI) or a shorter (ShTI) TI. Clinical cohort parameters were analyzed on a group of patients widely diverging for TI duration (<9 versus >18 months) on samples before TI, including NK-cell analysis and function by natural cytotoxicity receptor (NCR)-triggered -IFN production. Although persistently reduced NCR expression (NKp30) and fu... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411969 Fri, 28 Jan 2011 00:00:00 +0100 4411969 Activation of pulmonary invariant NKT cells leads to exacerbation of acute lung injury caused by LPS through local production of IFN-{gamma} and TNF-{alpha} by Gr-1+ monocytes http://www.medworm.com/index.php?rid=4411968&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F97%3Frss%3D1 Invariant NK T (iNKT) cells are known to play a critical role in the regulation of inflammatory responses in various clinical settings. In the present study, we assessed the contribution of iNKT cells to the development of acute lung injury (ALI), which was caused by intra-tracheal administration of LPS. J18 gene-disrupted mice lacking these cells underwent neutrophilic inflammatory responses in lungs at an equivalent level as control mice. Next, mice were sensitized intra-tracheally with -galactosylceramide, an activator of iNKT cells, followed by challenge with LPS. In this model, mice showed severe lung injury, and all mice were killed within 72 h after LPS injection. IFN- and tumor necrosis factor (TNF)- were strikingly elevated in the lungs of these mice. Administration of neutralizin... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411968 Fri, 28 Jan 2011 00:00:00 +0100 4411968 TLR2 deficiency by compromising p19 (IL-23) expression limits Th 17 cell responses to Mycobacterium tuberculosis http://www.medworm.com/index.php?rid=4411967&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F89%3Frss%3D1 CD4+ Th1 cells producing IFN- are of extreme importance in controlling infections by Mycobacterium tuberculosis both in mice and in men. In addition to IFN--producing T cells, IL-17-producing T cells (Th17) have been observed during mycobacterial infections. Nevertheless, their contribution for the host immune response to mycobacteria as well as the signals triggering M. tuberculosis -specific Th17 cell differentiation and maintenance are not fully understood. We show that signaling via Toll-like receptor (TLR) 2 has a major impact on the regulation of p19 (IL-23) expression in response to M. tuberculosis and therefore on the establishment of Th17 cell responses to M. tuberculosis infection. Diminished Th17 responses in the lung of M. tuberculosis -infected TLR2-deficient animals were not ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411967 Fri, 28 Jan 2011 00:00:00 +0100 4411967 Fas (CD95/APO-1) limits the expansion of T lymphocytes in an environment of limited T-cell antigen receptor/MHC contacts http://www.medworm.com/index.php?rid=4411966&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2F75%3Frss%3D1 Fas-deficient mice (Faslpr/lpr) and humans have profoundly dysregulated T lymphocyte homeostasis, which manifests as an accumulation of CD4+ and CD8+ T cells as well as an unusual population of CD4–CD8–TCRβ+ T cells. To date, no unifying model has explained both the increased T-cell numbers and the origin of the CD4–CD8–TCRβ+ T cells. As Faslpr/lpr mice raised in a germ-free environment still manifest lymphadenopathy, we considered that this process is primarily driven by recurrent low-avidity TCR signaling in response to self-peptide/MHC as occurs during homeostatic proliferation. In these studies, we developed two independent systems to decrease the number of self-peptide/MHC contacts. First, expression of MHC class I was reduced in OT-I TCR transgenic m... International Immunology journals http://www.medworm.com/rss/comments.php?id=4411966 Fri, 28 Jan 2011 00:00:00 +0100 4411966 In this issue http://www.medworm.com/index.php?rid=4411965&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F2%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4411965 Fri, 28 Jan 2011 00:00:00 +0100 4411965 Successful differentiation to T cells, but unsuccessful B-cell generation, from B-cell-derived induced pluripotent stem cells http://www.medworm.com/index.php?rid=4266644&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F1%2F65%3Frss%3D1 Forced expression of certain transcription factors in somatic cells results in generation of induced pluripotent stem (iPS) cells, which differentiate into various cell types. We investigated T-cell and B-cell lineage differentiation from iPS cells in vitro. To evaluate the impact of iPS cell source, murine splenic B-cell-derived iPS (B-iPS) cells were generated after retroviral transduction of four transcription factors (Oct4, Sox2, Klf4 and c-Myc). B-iPS cells were identical to embryonic stem (ES) cells and mouse embryonic fibroblast (MEF)-derived iPS cells in morphology, ES cell marker expression as well as teratoma and chimera mouse formation. Both B-iPS and MEF-derived iPS cells differentiated into lymphocytes in OP9 co-culture systems. Both efficiently differentiated into T-cell line... International Immunology journals http://www.medworm.com/rss/comments.php?id=4266644 Fri, 17 Dec 2010 00:00:00 +0100 4266644 Immature single-positive CD8+ thymocytes represent the transition from Notch-dependent to Notch-independent T-cell development http://www.medworm.com/index.php?rid=4266643&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F1%2F55%3Frss%3D1 Early in T-cell development, cells proceed through stages that are critically dependent on signaling through the Notch receptor. As cells mature, thymocytes transition from being Notch dependent to being Notch independent, but the stage of development during which this transition occurs is unknown. We used an in vitro differentiation system in which thymocytes can be cultured in the presence or absence of a Notch ligand to identify the stage of development in which thymocytes transition from being Notch responsive to Notch non-responsive. We identified the immature single-positive (ISP) CD8+ stage of T-cell development as being this transition point. ISP thymocytes were responsive to Notch, but ISP cells responded to Notch ligation in a manner that was distinct from the response by double-... International Immunology journals http://www.medworm.com/rss/comments.php?id=4266643 Fri, 17 Dec 2010 00:00:00 +0100 4266643 FCRLA is a resident endoplasmic reticulum protein that associates with intracellular Igs, IgM, IgG and IgA http://www.medworm.com/index.php?rid=4266642&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F1%2F43%3Frss%3D1 Fc receptor-like A (FCRLA) is an unusual member of the extended Fc receptor family. FCRLA has homology to receptors for the Fc portion of Ig (FCR) and to other FCRL proteins. However, unlike these other family representatives, which are typically transmembrane receptors with extracellular ligand-binding domains, FCRLA has no predicted transmembrane domain or N-linked glycosylation sites and is an intracellular protein. We show by confocal microscopy and biochemical assays that FCRLA is a soluble resident endoplasmic reticulum (ER) protein, but it does not possess the amino acid sequence KDEL as an ER retention motif in its C-terminus. Using a series of deletion mutants, we found that its ER retention is most likely mediated by the amino terminal partial Ig-like domain. We have identified E... International Immunology journals http://www.medworm.com/rss/comments.php?id=4266642 Fri, 17 Dec 2010 00:00:00 +0100 4266642 IL-23-dependent and -independent enhancement pathways of IL-17A production by lactic acid http://www.medworm.com/index.php?rid=4266641&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F1%2F29%3Frss%3D1 Interleukin-17A (IL-17A) is a cytokine produced by Th17 cells that plays an important role in inflammatory and autoimmune diseases and cancer. Stimulation with IL-6, transforming growth factor-β , IL-21, IL-1β and IL-23 is required for differentiation of Th17 cells and the production of IL-17A. Recently, we reported that tumor-derived lactic acid enhances the toll-like receptor (TLR) ligand-mediated expression of IL-23, leading to increased IL-17A production. Tumor cells secrete large amounts of lactic acid due to the up-regulation of glycolysis, which is known as the Warburg effect. Even without TLR ligand stimulation, lactic acid enhanced antigen-dependent IL-17A production from splenocytes in an IL-23-dependent manner. Here, we show that macrophages and effector/memory CD4+ T ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4266641 Fri, 17 Dec 2010 00:00:00 +0100 4266641 CD4+CD25-mTGF{beta}+ T cells induced by nasal application of ovalbumin transfer tolerance in a therapeutic model of asthma http://www.medworm.com/index.php?rid=4266640&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F1%2F17%3Frss%3D1 Conclusion: Nasal application of OVA in established asthma led to the induction of CD4+CD25–mTGFβ+ T cells with regulatory properties, able to confer protection upon allergen re-exposure. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4266640 Fri, 17 Dec 2010 00:00:00 +0100 4266640 Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma http://www.medworm.com/index.php?rid=4266639&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F1%2F1%3Frss%3D1 Signal transducer and activator of transcription (STAT)-3 inhibitors play an important role in regulating immune responses. Galiellalactone (GL) is a fungal secondary metabolite known to interfere with the binding of phosphorylated signal transducer and activator of transcription (pSTAT)-3 as well of pSTAT-6 dimers to their target DNA in vitro. Intra nasal delivery of 50 µg GL into the lung of naive Balb/c mice induced FoxP3 expression locally and IL-10 production and IL-12p40 in RNA expression in the airways in vivo. In a murine model of allergic asthma, GL significantly suppressed the cardinal features of asthma, such as airway hyperresponsiveness, eosinophilia and mucus production, after sensitization and subsequent challenge with ovalbumin (OVA). These changes resulted in inducti... International Immunology journals http://www.medworm.com/rss/comments.php?id=4266639 Fri, 17 Dec 2010 00:00:00 +0100 4266639 In this issue http://www.medworm.com/index.php?rid=4266638&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F23%2F1%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4266638 Fri, 17 Dec 2010 00:00:00 +0100 4266638 Partial NK cell tolerance induced by radioresistant host cells in rats transplanted with MHC-mismatched bone marrow http://www.medworm.com/index.php?rid=4253060&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F12%2F973%3Frss%3D1 We have studied the effect of radioresistant host cells in inducing tolerance and adaptation of the MHC recognition repertoire of donor-derived NK cells in stem cell allotransplanted (allo-SCT) rats. Sub-lethally irradiated PVG.1AV1 rats (RT1av1) were transplanted with bone marrow from fully MHC-mismatched allotype-marked PVG.7B (RT1c) rats; MHC-identical PVG (RT1c) controls were transplanted in parallel. In the PVG.7B -> PVG.1AV1 allogeneic chimeras, NK cells were donor derived and showed partial tolerance toward host cells. Allogeneic chimeras failed to efficiently reject PVG.1AV1 cells by an NK-mediated mechanism in vivo (allogeneic lymphocyte cytotoxicity), and IL-2-cultured NK cells derived from these chimeras showed diminished cytolytic activity against PVG.1AV1 cells in vitro. Th... International Immunology journals http://www.medworm.com/rss/comments.php?id=4253060 Mon, 13 Dec 2010 00:00:00 +0100 4253060 HEBAlt enhances the T-cell potential of fetal myeloid-biased precursors http://www.medworm.com/index.php?rid=4253059&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F12%2F963%3Frss%3D1 Hematopoiesis is controlled by the interplay between transcription factors and environmental signals. One of the primary determinants of the T-lineage choice is Delta-like (DL)-Notch signaling, which promotes T-cell development and inhibits B-cell development. We have found that the transcription factor HEBAlt is up-regulated in early hematopoietic precursors in response to DL-Notch signaling and that it can promote early T-cell development. Here, we identified a population of lineage-negative Sca-1–c-kit+ (LK) cells in the mouse fetal liver that rapidly gave rise to myeloid cells and B cells but exhibited very little T-cell potential. However, forced expression of HEBAlt in these precursors restored their ability to develop into T cells. We also showed that Ikaros and Notch1 are up-... International Immunology journals http://www.medworm.com/rss/comments.php?id=4253059 Mon, 13 Dec 2010 00:00:00 +0100 4253059 Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10 http://www.medworm.com/index.php?rid=4253058&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F12%2F953%3Frss%3D1 In this study, we examined the properties of macrophages in the colonic lamina propria (LM). Colonic DCs (LDC) showed LPS-induced production of IL-12p40. In contrast, LM showed constitutive IL-10 production and unresponsiveness to LPS in terms of inflammatory cytokine production. Comparison of the gene expression profiles between LM and LDC revealed that LM preferentially expressed IL-10-related genes. LM obtained from mice lacking IL-10 or Stat3 showed hyperproduction of tumour necrosis factor (TNF)- and IL-6 in response to LPS. IL-10 production in the large intestine was mainly induced by LM and regulatory T cells and was dependent on the presence of commensal microbiota. Accordingly, LM from germ-free mice showed less production of IL-10 and increased levels of LPS-induced TNF- and IL-6... International Immunology journals http://www.medworm.com/rss/comments.php?id=4253058 Mon, 13 Dec 2010 00:00:00 +0100 4253058 Production of IFN-{gamma} by CD4+ T cells in response to malaria antigens is IL-2 dependent http://www.medworm.com/index.php?rid=4253057&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F12%2F941%3Frss%3D1 We examined the regulation of CD4+ T-cell cytokine responses during infection with Plasmodium berghei ANKA (PbA). CD4+ T cells from PbA-infected mice produced IFN-, IL-4 and IL-10 in response to TCR stimulation at levels higher than those from uninfected mice. This altered cytokine response was dependent on parasitemia. To examine the specificity of the response, mice were adoptively transferred with CD4+ T cells from OT-II TCR transgenic mice and were infected with PbA expressing OVA. Unexpectedly, CD4+ T cells from the OT-II-transferred wild-type PbA-infected mice showed high levels of IFN- production after stimulation with OVA and the cells producing IFN- were not OT-II but were host CD4+ T cells. Further investigation revealed that host CD4+ T cells produced IFN- in response to IL-2 pr... International Immunology journals http://www.medworm.com/rss/comments.php?id=4253057 Mon, 13 Dec 2010 00:00:00 +0100 4253057 Evaluation of the immunoregulatory activity of intraepithelial lymphocytes in a mouse model of chronic intestinal inflammation http://www.medworm.com/index.php?rid=4253056&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F12%2F927%3Frss%3D1 The objective of this study was to examine the suppressive activity of IELs in vitro and in vivo using a mouse model of chronic small and large bowel inflammation. Adoptive transfer of CD8+ IELs isolated from small intestines of wild-type (WT) mice into TCR βx-deficient (TCR βx–/–) recipients did not prevent or delay the onset of the disease induced by WT CD4+CD45RBhigh T cells. On the contrary, we observed a more rapid onset of wasting and clinical signs of intestinal inflammation when compared with animals injected with CD4+CD45RBhigh T cells alone. Histopathological scores of small and large bowel did not differ significantly between the two groups. Transfer of IELs alone did not produce any pathological changes. Real-time PCR analysis of intestinal tissues showed ... International Immunology journals http://www.medworm.com/rss/comments.php?id=4253056 Mon, 13 Dec 2010 00:00:00 +0100 4253056 PD-1-PD-L1 pathway impairs Th1 immune response in the late stage of infection with Mycobacterium bovis bacillus Calmette-Guerin http://www.medworm.com/index.php?rid=4253055&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F12%2F915%3Frss%3D1 A major concern still prevails as to the reason why various mycobacteria are able to persist within infected host in which protective immunity is generated. To address this question, we monitored the generation of protective T cells during infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). CD4+ T cells obtained 3 weeks after infection conferred protection against Mycobacterium tuberculosis challenge and produced IFN- and tumor necrosis factor (TNF)- upon antigen stimulation. However, these abilities were decreased after 6 weeks of infection even though BCG was not thoroughly eliminated from the host. We analyzed the expression of ligands for the CD28/CTLA-4 family receptors on antigen-presenting cells and found that the expression of PD-L1, a ligand for programmed ce... International Immunology journals http://www.medworm.com/rss/comments.php?id=4253055 Mon, 13 Dec 2010 00:00:00 +0100 4253055 In this issue http://www.medworm.com/index.php?rid=4253054&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F12%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4253054 Mon, 13 Dec 2010 00:00:00 +0100 4253054 Invariant NKT cell anergy is induced by a strong TCR-mediated signal plus co-stimulation http://www.medworm.com/index.php?rid=4213953&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F11%2F905%3Frss%3D1 In this study, we monitor how iNKT anergy is induced. Anergized iNKT cells dramatically reduced the expression of IL-2R, and exogenous IL-2 restored the ability to proliferate and produce IL-4 but not to produce IFN-. Anergized iNKT cells expressed high levels of programmed death-1 (PD-1). However, iNKT cells in PD-1-deficient mice became anergic as a result of GC injection, as do normal mice. Furthermore, anti-PD-1 blocking mAb was unable to restore their responsiveness. When iNKT cells were stimulated with immobilized anti-CD3 in the presence or absence of anti-CD28, they produced cytokines in a dose-dependent manner. Unlike in naive CD4 T cells, the strong TCR-mediated signaling with co-stimulation renders them anergic to any subsequent stimulation with GC and spleen dendritic cells (DC... International Immunology journals http://www.medworm.com/rss/comments.php?id=4213953 Tue, 30 Nov 2010 00:00:00 +0100 4213953 Structural characterization of the TCR complex by electron microscopy http://www.medworm.com/index.php?rid=4213952&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F11%2F897%3Frss%3D1 In this study, we have purified the TCR from T cells under native conditions and used electron microscopy to derive a three-dimensional structure. The TCR complex appears as a pear-shaped structure of 180 x 120 x 65 . Furthermore, the use of mAbs has allowed to determine the orientation of the TCR/β and CD3 subunits and to suggest a model of interactions. Interestingly, the reconstructed TCR is larger than expected for a complex with a β stoichiometry. The accommodation of a second TCRβ to fill in the extra volume is discussed. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4213952 Tue, 30 Nov 2010 00:00:00 +0100 4213952 The Candida Th17 response is dependent on mannan- and {beta}-glucan-induced prostaglandin E2 http://www.medworm.com/index.php?rid=4213951&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F11%2F889%3Frss%3D1 In this study, we have investigated the role of PGE2 in the Th17 response induced by C. albicans in humans. PBMC were stimulated with C. albicans in the absence or presence of a non-steroidal anti-inflammatory drug (NSAID). In separate experiments, PGE2 or the prostlaglandin receptors agonists butaprost or misoprostol were added to the cells. PBMC were also stimulated with fungal components and small interfering RNA for mannose receptor (MR) was performed. PGE2 and cytokines were measured by ELISA or luminex, and the source of IL-17 production was determined using FACS analysis. Blocking Candida-induced PGE2 production by an NSAID resulted in decreased IL-17 and IL-22 production and inhibited expression of RAR-related orphan receptor gamma T mRNA. Furthermore, when PGE2 production was bloc... International Immunology journals http://www.medworm.com/rss/comments.php?id=4213951 Tue, 30 Nov 2010 00:00:00 +0100 4213951 Ig gene diversification and selection in follicular lymphoma, diffuse large B cell lymphoma and primary central nervous system lymphoma revealed by lineage tree and mutation analyses http://www.medworm.com/index.php?rid=4213950&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F11%2F875%3Frss%3D1 Follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL) and primary central nervous system lymphoma are B cell malignancies. FL and DLBCL have a germinal center origin. We have applied mutational analyses and a novel algorithm for quantifying shape properties of mutational lineage trees to investigate the nature of the diversification, somatic hypermutation and selection processes that affect B cell clones in these malignancies and reveal whether they differ from normal responses. Lineage tree analysis demonstrated higher diversification and mutations per cell in the lymphoma clones. This was caused solely by the longer diversification times of the malignant clones, as their recent diversification processes were similar to those of normal responses, implying similar mutation freque... International Immunology journals http://www.medworm.com/rss/comments.php?id=4213950 Tue, 30 Nov 2010 00:00:00 +0100 4213950 A panel of human cell-based artificial APC enables the expansion of long-lived antigen-specific CD4+ T cells restricted by prevalent HLA-DR alleles http://www.medworm.com/index.php?rid=4213949&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F11%2F863%3Frss%3D1 Many preclinical experiments have attested to the critical role of CD4+ T cell help in CD8+ cytotoxic T lymphocyte (CTL)-mediated immunity. Recent clinical trials have demonstrated that reinfusion of CD4+ T cells can induce responses in infectious diseases and cancer. However, few standardized and versatile systems exist to expand antigen-specific CD4+ Th for clinical use. K562 is a human erythroleukemic cell line, which lacks expression of HLA class I and class II, invariant chain and HLA-DM but expresses adhesion molecules such as intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. With this unique immunologic phenotype, K562 has been tested in clinical trials of cancer immunotherapy. Previously, we created a K562-based artificial antigen-presenting cell (aAPC)... International Immunology journals http://www.medworm.com/rss/comments.php?id=4213949 Tue, 30 Nov 2010 00:00:00 +0100 4213949 Role of the NF-{kappa}B transcription factor c-Rel in the generation of CD8+ T-cell responses to Toxoplasma gondii http://www.medworm.com/index.php?rid=4213948&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F11%2F851%3Frss%3D1 The nuclear factor B transcription factor c-Rel is exclusively expressed in immune cells and plays a role in numerous cellular functions including proliferation, survival and production of chemokines and cytokines. c-Rel has also been implicated in the regulation of multiple genes involved in innate and adaptive immune responses to the intracellular protozoan parasite Toxoplasma gondii, in particular IL-12. To better understand how this transcription factor controls the CD8+ T-cell response to this organism, wild-type (WT) and c-Rel–/– mice were challenged with a replication-deficient strain of T. gondii that expresses the model antigen ovalbumin (OVA). These studies revealed that c-Rel was required for optimal primary expansion of OVA-specific CD8+ T cells and that immunized c... International Immunology journals http://www.medworm.com/rss/comments.php?id=4213948 Tue, 30 Nov 2010 00:00:00 +0100 4213948 In this issue http://www.medworm.com/index.php?rid=4213947&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F11%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4213947 Tue, 30 Nov 2010 00:00:00 +0100 4213947 Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration http://www.medworm.com/index.php?rid=4003640&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F10%2F839%3Frss%3D1 Tissue inflammation induces rapid mobilization of antigen-charged dendritic cells (DCs), which migrate to draining lymph nodes via afferent lymphatics to elicit the immune response. This increase in DC trafficking has been shown to require integrin-dependent adhesion to ICAM-1 and VCAM-1, expressed on inflamed lymphatic endothelium. In addition, both constitutive- and inflammation-induced DC migration involves the chemokine CCL21, which most likely triggers integrin activation on DC via its receptor CCR7. Recently, however, conflicting evidence has suggested that DC entry occurs independently of integrins, implying that the role of CCL21 in lymphatics is purely chemotactic. Hence, while CCL21 is reported to be inducible during inflammation, the details of this induction and the role of CCL... International Immunology journals http://www.medworm.com/rss/comments.php?id=4003640 Mon, 27 Sep 2010 14:47:26 +0100 4003640 Neutrophil activation and survival are modulated by interaction with NK cells http://www.medworm.com/index.php?rid=4003638&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F10%2F827%3Frss%3D1 In this study, we analyzed whether human NK cells may influence the survival and activation of neutrophils under co-culture conditions. We report that NK cells exposed to either IL-15 or IL-18 alone strongly protect the survival of neutrophils via the release of IFN and granulocyte macrophage colony-stimulating factor (GM-CSF) plus IFN, respectively, and cause a slight up-regulation of neutrophil CD64 and CD11b expression. In comparison, NK cells exposed to both IL-15 and IL-18 show a lesser ability to increase the survival of neutrophils but can more potently up-regulate CD64 and CD11b expression, as well as induce the de novo surface expression of CD69, in neutrophils. Analysis of the events occurring in neutrophil/NK co-cultures exposed to IL-15 plus IL-18 revealed that (i) neutrophil s... International Immunology journals http://www.medworm.com/rss/comments.php?id=4003638 Mon, 27 Sep 2010 14:47:26 +0100 4003638 Targeting ganglioside epitope 3G11 on the surface of CD4+ T cells suppresses EAE by altering the Treg/Th17 cell balance http://www.medworm.com/index.php?rid=4003636&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F10%2F817%3Frss%3D1 Loss of expression of the 3G11 epitope, present on disialoceramide that is predominantly found on CD4+ T cells, has been associated with a regulatory T cell (Treg) phenotype and tolerance induction in experimental autoimmune encephalomyelitis (EAE). Here we report that treatment with anti-3G11 mAb shifts the immune response from pro-inflammatory to tolerogenic and suppresses both chronic-progressive and relapsing–remitting EAE. This therapeutic effect can be achieved at different stages of EAE. Treatment with anti-3G11 mAb increased the proportion of Foxp3+CD25+CD4+ Tregs and IL-10 production while inhibiting production of pro-inflammatory cytokines and responsiveness to IL-2 and decreasing the proportion of Th17 cells. The effect of anti-3G11 mAb was diminished in IL-10–/&ndas... International Immunology journals http://www.medworm.com/rss/comments.php?id=4003636 Mon, 27 Sep 2010 14:47:26 +0100 4003636 IL-1 plays an important role in the bone metabolism under physiological conditions http://www.medworm.com/index.php?rid=4003634&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F10%2F805%3Frss%3D1 In this study, we addressed the role of IL-1 in physiological bone metabolism through analyses of IL-1-deficient (KO), IL-1β KO and IL-1/β double KO mice that were housed under specific pathogen free conditions. The femur mineral density, trabecular bone mass and cortical thickness significantly increased in all KO mice compared with wild-type (WT) mice. The number of osteoclasts in trabecular bones decreased, suggesting that IL-1 regulates bone metabolism through regulation of osteoclast formation. When differentiation of bone marrow (BM) cells into osteoclasts was induced by parathyroid hormone in co-cultures of osteoblasts and BM cells from WT and IL-1/β KO mice, IL-1/β KO BM cell co-cultures failed to undergo efficient osteoclast-like multinucleated cell (OCL) diffe... International Immunology journals http://www.medworm.com/rss/comments.php?id=4003634 Mon, 27 Sep 2010 14:47:26 +0100 4003634 Making memories that last a lifetime: heritable functions of self-renewing memory CD8 T cells http://www.medworm.com/index.php?rid=4003535&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F10%2F797%3Frss%3D1 Clonal expansion of virus-specific naive T cells during an acute viral infection results in the formation of memory CD8 T cells that provide the host with long-term protective immunity against the pathogen. Memory CD8 T cells display enhanced effector functions compared with their naive precursors, allowing them to respond more rapidly and effectively to antigen re-encounter. The enhanced functions of memory CD8 T cells are mediated by heritable changes in gene regulation. Expression of select transcription factors along with locus-specific epigenetic modifications are coupled to and are essential in the formation of memory-specific gene expression patterns. Here, we will review the changes in gene expression that accompany development of memory CD8 T cells and discuss chromatin modificati... International Immunology journals http://www.medworm.com/rss/comments.php?id=4003535 Mon, 27 Sep 2010 14:47:26 +0100 4003535 The network of transcription factors that underlie the CD4 versus CD8 lineage decision http://www.medworm.com/index.php?rid=4003534&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F10%2F791%3Frss%3D1 This article describes their antagonistic interaction that is an important mechanism of the lineage specification, as well as the hierarchy and importance of several other transcription factors and cytokine signals in the network of pathways that govern thymocyte helper/cytotoxic lineage commitment. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4003534 Mon, 27 Sep 2010 14:47:26 +0100 4003534 In this issue http://www.medworm.com/index.php?rid=4003476&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F10%2FNP%3Frss%3D1 (No abstract is available for this citation) (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=4003476 Mon, 27 Sep 2010 14:47:26 +0100 4003476 Tumor cells of non-hematopoietic and hematopoietic origins express activation-induced C-type lectin, the ligand for killer cell lectin-like receptor F1 http://www.medworm.com/index.php?rid=3904305&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F783%3Frss%3D1 In this study, we show that activation-induced C-type lectin (AICL) is a unique KLRF1 ligand expressed on tumor cell lines of hematopoietic and non-hematopoietic origins. We screened a panel of human tumor cell lines using the KLRF1 reporter cells and found that several tumor lines expressed KLRF1 ligands. We characterized a putative KLRF1 ligand expressed on the U937 cell line. The molecular mass for the deglycosylated ligand was 28 kDa under non-reducing condition and 17 kDa under reducing condition, suggesting that the KLRF1 ligand is a homodimer. By expression cloning from a U937 cDNA library, we identified AICL as a KLRF1 ligand. We generated mAbs against AICL to identify the KLRF1 ligands on non-hematopoietic tumor lines. The anti-AICL mAbs stained the tumor lines that express the KL... International Immunology journals http://www.medworm.com/rss/comments.php?id=3904305 Thu, 26 Aug 2010 15:25:09 +0100 3904305 Increased IgG1, IFN-{gamma}, TNF-{alpha} and IL-6 responses to Mycobacterium tuberculosis antigens in patients with Tuberculosis are lower after chemotherapy http://www.medworm.com/index.php?rid=3904304&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F775%3Frss%3D1 Detection of specific antibodies may represent an additional tool in diagnosis of tuberculosis (TB). Herein, levels of serum IgG antibodies against early secreted antigenic target (ESAT-6), culture filtrate antigen-10 (CFP-10) and 16kDa Mycobacterium tuberculosis antigens were measured in 33 active pulmonary TB patients (0M-TB), in 47 patients after 1–3 months of treatment (3M-TB) and in 22 patients who had completed 6 months of chemotherapy (6M-TB). The control group consisted of 38 BCG-vaccinated healthy controls (HC). In addition, IFN-, tumor necrosis factor (TNF)-, IL-6, IL-2, IL-4 and IL-10 production in PBMC cultures from 20 patients were measured following stimulation with the M. tuberculosis-specific fusion protein ESAT-6/CFP-10. Elevated levels of IgG against ESAT-6, CFP-10 ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3904304 Thu, 26 Aug 2010 15:25:09 +0100 3904304 T-lymphocyte calcium influx characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in the neonate http://www.medworm.com/index.php?rid=3904303&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F769%3Frss%3D1 Cytokine production in activated T lymphocytes of the term neonate is reduced compared with adults. We aimed to characterize the calcium influx kinetics of activated T lymphocytes in the neonate and to test the functionality and expression of Kv1.3 and IKCa1 lymphocyte potassium channels, important regulators of calcium influx. We isolated lymphocytes from the peripheral blood of nine adults and cord blood of nine term neonates. We measured the calcium influx kinetics with flow cytometry in the Th1, Th2, CD4 and CD8 T-lymphocyte subsets activated with PHA. We determined the sensitivity of calcium influx to specific inhibitors of the Kv1.3 and IKCa1 channels. We also measured Kv1.3 channel expression using specific antibody. With the exception of the CD4 subset, calcium influx kinetics was ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3904303 Thu, 26 Aug 2010 15:25:08 +0100 3904303 Antigen-specific activation thresholds of CD8+ T cells are independent of IFN-I-mediated partial lymphocyte activation http://www.medworm.com/index.php?rid=3904302&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F757%3Frss%3D1 Type-I IFN (IFN-I) are highly pleiotropic cytokines known to modulate immune responses and play an early central role in mediating antiviral defenses. We have shown that IFN-I mediate transient up-regulation of a distinct subset of lymphocyte surface activation markers on both B and T cells in vivo independent of cognate antigen: a state referred to as ‘partial lymphocyte activation’. Here we investigated in vitro the possibility that partial lymphocyte activation may serve to lower the antigen-specific activation thresholds for T cells. We found that the kinetics of Ca2+ flux in T cells responding to TCR cross-linking was not enhanced in partially activated T cells. Furthermore, following TCR stimulation with anti-cluster of differentiation (CD) 3, a lower proportion of partia... International Immunology journals http://www.medworm.com/rss/comments.php?id=3904302 Thu, 26 Aug 2010 15:25:08 +0100 3904302 Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes http://www.medworm.com/index.php?rid=3904300&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F749%3Frss%3D1 In conclusion, the adaptive immune systems are essential for elimination of rLCMV/VSVG, and type I but not type II IFN plays a major contributive role in lowering rLCMV/VSVG loads in vivo, attesting to the attenuation profile of the vaccine. Nevertheless, IFNs are not required for the induction of potent vaccine responses. These results provide a better understanding of the immunobiology of rLCMV/VSVG and will contribute to the further development of GP exchange vaccines for combating arenaviral hemorrhagic fevers. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3904300 Thu, 26 Aug 2010 15:25:08 +0100 3904300 Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells http://www.medworm.com/index.php?rid=3904299&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F739%3Frss%3D1 In this study, we took advantage of UT12 to generate prolonged ET to explore the possibility that ET is involved in the inhibitory effects of the TLR4 signals on asthma model mice. Induction of ET by UT12 inhibited the capacity of DCs to expand ovalbumin (OVA)-specific Th2 and Th17 cells, without inducing Th1 cell or regulatory T-cell populations or producing inhibitory cytokines. Accordingly, administration of UT12 before the OVA sensitization significantly suppressed airway allergic inflammation by OVA inhalation. Taken together, these results demonstrate that ET induced by activating TLR4 signals attenuates airway allergic inflammation through direct suppression of the T-cell stimulatory effect of DCs in asthma model mice. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3904299 Thu, 26 Aug 2010 15:25:08 +0100 3904299 Ameliorating effects of anti-Dll4 mAb on Theiler's murine encephalomyelitis virus-induced demyelinating disease http://www.medworm.com/index.php?rid=3904298&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F729%3Frss%3D1 We examined the role of Notch ligand Delta-like 4 (Dll4) in the development of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD). Treatment with mAb to Dll4, especially during the effector phase, resulted in significant suppression of the disease development both clinically and histologically. The number of infiltrating mononuclear inflammatory cells in the spinal cords was also decreased in mice treated with anti-Dll4 mAb. Semi-quantitative analysis of mRNA by using real-time PCR revealed that mRNAs of Th1-derived cytokines such as IFN- and Th17-derived cytokines such as IL-17 were decreased in mice treated with anti-Dll4 mAb, whereas those of Th2-derived cytokines such as IL-4 and IL-10 were not. Flow cytometric analysis of cytokines indicated that ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3904298 Thu, 26 Aug 2010 15:25:08 +0100 3904298 Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome-related mRNAs in humans and mice http://www.medworm.com/index.php?rid=3904297&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2F717%3Frss%3D1 The cell-type-, organ- and species-specific expression of the surface and endosomally located Toll-like receptors are well described but little is known about the respective expression profiles of cytosolic pattern recognition molecules. We therefore determined the mRNA expression levels of 15 cytosolic pattern recognition molecules in 11 solid organs of human and mice. Human organs revealed lower mRNA levels of most molecules as in spleen but at least 2-fold higher were inflammasome-related NOD, leucine-rich repeat and pyrin domain-containing protein 1–3 (NLRP1–3) and -12 in brain, LGP2, retinoic acid-inducible gene I (RIG-I) and NLRP10 in liver, NLRP10 in small intestine, LGP2, RIG-I, NAIP, NLRP2 and -3 in testis and RIG-I, NLRP2 and -10 in muscle. In mice, most organs also e... International Immunology journals http://www.medworm.com/rss/comments.php?id=3904297 Thu, 26 Aug 2010 15:25:08 +0100 3904297 In this issue http://www.medworm.com/index.php?rid=3904296&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F9%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3904296 Thu, 26 Aug 2010 15:25:08 +0100 3904296 I-Ag7 is subject to post-translational chaperoning by CLIP http://www.medworm.com/index.php?rid=3777691&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F705%3Frss%3D1 Several MHC class II alleles linked with autoimmune diseases form unusually low-stability complexes with class II-associated invariant chain peptides (CLIP), leading us to hypothesize that this is an important feature contributing to autoimmune pathogenesis. We recently demonstrated a novel post-endoplasmic reticulum (ER) chaperoning role of the CLIP peptides for the murine class II allele I-Ed. In the current study, we tested the generality of this CLIP chaperone function using a series of invariant chain (Ii) mutants designed to have varying CLIP affinity for I-Ag7. In cells expressing these Ii CLIP mutants, I-Ag7 abundance, turnover and antigen presentation are all subject to regulation by CLIP affinity, similar to I-Ed. However, I-Ag7 undergoes much greater quantitative changes than ob... International Immunology journals http://www.medworm.com/rss/comments.php?id=3777691 Thu, 22 Jul 2010 15:45:31 +0100 3777691 Accessibility control of TCR V{gamma} region by STAT5 http://www.medworm.com/index.php?rid=3777690&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F693%3Frss%3D1 The signal of the IL-7R and signal transducers and activators of transcription (STAT) 5 plays an essential role in T-cell development by inducing V–J recombination in the TCR locus. Previously, we have shown that STAT5 binds to the J promoters and controls chromatin accessibility by histone acetylation. However, little is known on control mechanism of V region by the IL-7R. To elucidate the regulation by STAT5, we first analyzed the chromatin status of V region in primary thymocytes. The levels of histone H3 acetylation are high at V5, HsA element and V2 in Rag2–/– thymocytes but low in IL-7R -chain (IL-7R)-deficient early thymocytes, suggesting that IL-7R signaling controls the accessibility of the V region. In addition, high levels of histone H3 acetylation and germ lin... International Immunology journals http://www.medworm.com/rss/comments.php?id=3777690 Thu, 22 Jul 2010 15:45:31 +0100 3777690 B-cell homeostasis requires complementary CD22 and BLyS/BR3 survival signals http://www.medworm.com/index.php?rid=3777689&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F681%3Frss%3D1 Peripheral B-cell numbers are tightly regulated by homeostatic mechanisms that influence the transitional and mature B-cell compartments and dictate the size and clonotypic diversity of the B-cell repertoire. B-lymphocyte stimulator (BLyS, a trademark of Human Genome Sciences, Inc.) plays a key role in regulating peripheral B-cell homeostasis. CD22 also promotes peripheral B-cell survival through ligand-dependent mechanisms. The B-cell subsets affected by the absence of BLyS and CD22 signals overlap, suggesting that BLyS- and CD22-mediated survival are intertwined. To examine this, the effects of BLyS insufficiency following neutralizing BLyS mAb treatment in mice also treated with CD22 ligand-blocking mAb were examined. Combined targeting of the BLyS and CD22 survival pathways led to sign... International Immunology journals http://www.medworm.com/rss/comments.php?id=3777689 Thu, 22 Jul 2010 15:45:31 +0100 3777689 HIV-1 integrase-hydrolyzing IgM antibodies from sera of HIV-infected patients http://www.medworm.com/index.php?rid=3777688&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F671%3Frss%3D1 We present evidence showing that 22 of 24 (91.7%) IgMs purified from the sera of HIV-infected patients specifically hydrolyze only HIV IN but not many other tested proteins. Usually, proteolytic antibodies of AI patients are serine protease-like or metal dependent. Only 30% of IN-hydrolyzing IgMs were inhibited by specific inhibitors of serine proteases and 60% by inhibitors of metal-dependent proteases. Unusually, a significant reduction of the activity by specific inhibitors of acidic (in 20% of IgM preparations) and thiol proteases (in 100% of IgM preparations) was observed. Although HIV infection leads to formation of antibodies to many viral and human antigens, possible biological roles for most of them are unknown. Since anti-IN IgG can efficiently hydrolyze IN, a positive role of Ab... International Immunology journals http://www.medworm.com/rss/comments.php?id=3777688 Thu, 22 Jul 2010 15:45:31 +0100 3777688 Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis http://www.medworm.com/index.php?rid=3777687&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F661%3Frss%3D1 In conclusion, Con A induced autophagy on hepatic endothelial cells; the damage of liver blood vessel occurs before the induction of T-cell-dependent hepatitis via apoptosis or T-cell-independent hepatitis via autophagy. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3777687 Thu, 22 Jul 2010 15:45:31 +0100 3777687 PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1 http://www.medworm.com/index.php?rid=3777686&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F651%3Frss%3D1 The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete for PD-1 binding. PD-L1 and PD-L2 bound PD-1 with comparable affinities, but striking differences were observed at the level of the association and dissociation characteristics. PD-L1, but not PD-L2, had a delayed interaction reminiscent of a phenomenon of conformational transition. These mechanisms were confirmed by using PD-L1 mAbs that delayed the dissociation of PD-L1 from PD-1. This mechanism was... International Immunology journals http://www.medworm.com/rss/comments.php?id=3777686 Thu, 22 Jul 2010 15:45:31 +0100 3777686 MT6-MMP is present in lipid rafts and faces inward in living human PMNs but translocates to the cell surface during neutrophil apoptosis http://www.medworm.com/index.php?rid=3777685&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F637%3Frss%3D1 Polymorphonuclear neutrophils (PMNs) are the first line of defense against invading organisms in humans; in addition, PMNs contribute to the linking of innate and adaptive immunity. To fulfill their biological behavior, PMNs utilize an arsenal of proteolytic enzymes, including members of the matrix metalloproteinase family of zinc-dependent endopeptidases. PMNs express high levels of MT6-MMP (MMP-25), a glycosyl-phosphatidylinositol-anchored MMP, that belongs to the subfamily of membrane-anchored matrix metalloproteinases. Due to the paucity of information on MT6-MMP in primary cells, we set to investigate the localization and potential function of MT6-MMP in human PMNs. We found that MT6-MMP is present in the membrane, granules and nuclear/endoplasmic reticulum/Golgi fractions of PMNs whe... International Immunology journals http://www.medworm.com/rss/comments.php?id=3777685 Thu, 22 Jul 2010 15:45:31 +0100 3777685 NKT cells are necessary for maximal expression of allergic conjunctivitis1 http://www.medworm.com/index.php?rid=3777684&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F627%3Frss%3D1 Allergic conjunctivitis (AC) is elicited by immediate hypersensitivity responses to environmental agents. It is initiated by a Th2-dominated immune response that is characterized by production of IgE antibodies and eosinophilic infiltration. By using an experimental mouse model of AC induced by short ragweed (SRW) pollen, we show that sensitized J18–/– mice, which lack type I NKT cells, and CD1d–/– mice, which lack type I and type II NKT cells, exhibited a decrease in tearing, lid edema, conjunctival edema and vasodilatation and eosinophil infiltration into the conjunctiva when compared with wild-type (WT) mice in both Th1- and Th2-prone hosts (C57BL/6 and BALB/c mice, respectively). This demonstrates that NKT cells are needed for both the early and late phases of A... International Immunology journals http://www.medworm.com/rss/comments.php?id=3777684 Thu, 22 Jul 2010 15:45:31 +0100 3777684 Early events governing memory CD8+ T-cell differentiation http://www.medworm.com/index.php?rid=3777683&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2F619%3Frss%3D1 Understanding the regulation of the CD8+ T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8+ T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8+ T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8+ T cells. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3777683 Thu, 22 Jul 2010 15:45:31 +0100 3777683 In this issue http://www.medworm.com/index.php?rid=3777682&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F8%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3777682 Thu, 22 Jul 2010 15:45:31 +0100 3777682 Specific serum protein biomarkers of rheumatoid arthritis detected by MALDI-TOF-MS combined with magnetic beads http://www.medworm.com/index.php?rid=3696717&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F7%2F611%3Frss%3D1 Conclusions. The present data suggested that MALDI-TOF-MS combined with magnetic beads could screen and identify some novel serum protein biomarkers related to RA. The proteomic pattern based on the four candidate biomarkers is of value for laboratory diagnosis of RA. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3696717 Fri, 25 Jun 2010 14:46:44 +0100 3696717 Decreased human paraoxonase-1 activity in patients with Sjogren's syndrome http://www.medworm.com/index.php?rid=3696716&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F7%2F605%3Frss%3D1 Conclusions: Despite the relatively small sample size that reduces the power of the study, decreased PON activity may be a possible cardiovascular risk factor in SS. Disadvantageous PON1 phenotype distribution may contribute to the decreased PON activity in these patients. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3696716 Fri, 25 Jun 2010 14:46:44 +0100 3696716 Reducing glycosphingolipid biosynthesis in airway cells partially ameliorates disease manifestations in a mouse model of asthma http://www.medworm.com/index.php?rid=3696715&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F7%2F593%3Frss%3D1 In this study, we evaluated the impact of inhibiting GSL biosynthesis in mast cells and in the ovalbumin (OVA)-induced mouse model of asthma using either a small molecule inhibitor or anti-sense oligonucleotides (ASOs) directed against specific enzymes in the GSL pathway. Lowering GSL levels in mast cells through inhibition of glucosylceramide synthase (GCS) reduced phosphorylation of Syk tyrosine kinase and phospholipase C gamma 2 (PLC-2) as well as cytoplasmic Ca2+ levels. Modulating these intracellular signaling events also resulted in a significant decrease in mast cell degranulation. Primary mast cells isolated from a GM3 synthase (GM3S) knockout mouse exhibited suppressed activation-induced degranulation activity further supporting a role of GSLs in this process. In previously OVA-se... International Immunology journals http://www.medworm.com/rss/comments.php?id=3696715 Fri, 25 Jun 2010 14:46:44 +0100 3696715 MicroRNA 125b inhibition of B cell differentiation in germinal centers http://www.medworm.com/index.php?rid=3696714&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F7%2F583%3Frss%3D1 MicroRNAs 125a and 125b are predicted to be able to bind to the B lymphocyte-induced maturation protein-1 (BLIMP-1) and IFN regulatory protein-4 (IRF-4) transcription factors, which are essential for plasma cell differentiation. A computational survey of the human and mouse genomes revealed that miR-125a and miR-125b are members of a multigene family located in paralogous clusters. The miR-125a cluster on chromosome 19 in humans includes miR-99b and let-7e, whereas the miR-125b cluster on chromosome 21 includes miR-99a and miR-let-7c. Our analysis of the expression profiles for these six miRs during B lineage differentiation indicated that mature miR-125a, miR-125b, miR-99b and let-7e transcripts are preferentially expressed by the actively dividing centroblasts in germinal centers (GC). H... International Immunology journals http://www.medworm.com/rss/comments.php?id=3696714 Fri, 25 Jun 2010 14:46:44 +0100 3696714 The pathogenicity of self-antigen decreases at high levels of autoantigenicity: a computational approach http://www.medworm.com/index.php?rid=3696713&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F7%2F571%3Frss%3D1 Recent experimental evidence suggests that antigenic stability facilitates antigen shuttling from target tissue to dendritic cells (DCs), enabling cross-priming of naive T cells. On the other hand, antigenic stability affects the efficiency of peptide–MHC (p-MHC) complex formation, altering a target cell's susceptibility to killing by the resulting CTLs. Using a mathematical model, we show how antigenic stability and p-MHC production efficiency interplay in autoantigenicity and pathogenic potential of target cell proteins in autoimmune disease. We consider protein allocated to both rapidly degraded versus stable functional pools [fractions f, 1 – f], contributing, with relative efficiency , to p-MHC presentation on a target cell, as well as to cross-presentation on a DC; we ana... International Immunology journals http://www.medworm.com/rss/comments.php?id=3696713 Fri, 25 Jun 2010 14:46:43 +0100 3696713 Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphylococcus aureus proteins http://www.medworm.com/index.php?rid=3696712&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F7%2F561%3Frss%3D1 We previously reported that intranasal challenge with ovalbumin (OVA) plus IL-18 induces airway hyperresponsiveness (AHR) and eosinophilic airway inflammation in mice with OVA-specific Th1 cells. These two conditions can be prevented by neutralizing anti-IFN- and anti-IL-13 antibodies, respectively. The mice develop AHR and eosinophilic airway inflammation after challenge with OVA plus LPS instead of IL-18 and endogenous IL-18 is known to be involved. In contrast, IL-18 does not facilitate these changes in mice possessing OVA-specific Th2 cells. Here, we investigated whether IL-18 is involved in the development of asthma in mice immunized and challenged with bacterial proteins. Upon intranasal exposure to protein A (SpA) derived from Staphylococcus aureus, mice immunized with SpA exhibited... International Immunology journals http://www.medworm.com/rss/comments.php?id=3696712 Fri, 25 Jun 2010 14:46:43 +0100 3696712