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 'Clinical and Experimental Immunology' source. Wed, 08 Feb 2012 06:42:47 +0100 http://www.medworm.com/index.php?rid=5659219&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04570.x In this report, we showed that IL‐22 stimulated production of vascular endothelial growth factor (VEGF) and the anti‐apoptotic factor Bcl‐XL in IL‐22R‐positive HPAFII human pancreatic cancer cells. Additionally, IL‐22 augmented HPAFII cell production of immunosuppressive cytokines. We further showed that IL‐22 activation of HPAFII cells diminished T cell production of IFN‐γ through the action of IL‐10. Strikingly, we showed for the first time that IL‐22 can fully protect cancer cells from NK cell‐mediated cytotoxicity by stimulating tumor production of IL‐10 and TGF‐β1. Our data supports the idea that IL‐22 may act to promote the pathogenesis of cancers rather than function in anti‐tumor immunity.© 2012 The Authors. Clinical and Experimental Immunology © 2... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5659219 Sun, 05 Feb 2012 11:17:35 +0100 5659219 http://www.medworm.com/index.php?rid=5659220&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04569.x SummaryThe association between immune dysfunction and the development of autoimmune pathology in patients with HIV/AIDS is not clear. The frequency and phenotype of regulatory T cells, as well as the presence of autoantibodies were evaluated in a paediatric cohort of HIV‐infected patients without clinical evidence of autoimmune disease. Lower absolute counts but higher percentages of total CD4+FOXP3+ T cells were recorded in children with severe immunosuppression than in those without evidence of immunosuppression. The frequencies of classical CD4+CD25+FOXP3+regulatory T cells were not altered, whereas CD4+FOXP3+CD25–T cells were found significantly increased in patients with severe immunosuppression. Like classical regulatory T cells, CD4+FOXP3+CD25–T cells display higher CTLA‐4 b... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5659220 Fri, 03 Feb 2012 05:00:00 +0100 5659220 http://www.medworm.com/index.php?rid=5646600&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04536.x SummaryLeishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)‐γ‐producing CD4+T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of mult... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646600 Thu, 02 Feb 2012 11:18:45 +0100 5646600 http://www.medworm.com/index.php?rid=5646599&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04526.x SummaryIn patients with human immunodeficiency virus (HIV) infection, neutrophil and monocyte functions, including phagocytosis, are impaired. The purpose of this study was to investigate changes of phagocytic function and respiratory burst occurring over the course of patients infected by the HIV‐1 virus. Treatment‐naive patients (group B), patients receiving highly active anti‐retroviral treatment (HAART) (group C) and patients in which HAART has failed (group D) were studied and compared with healthy volunteers (group A). Phagocytosis and oxidative burst were evaluated using commercially available kits. Results clearly denote a significant decrease of the phagocytic function of both cell types of groups B and C compared with group A. Among group C patients, those in the upper quar... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646599 Thu, 02 Feb 2012 11:18:43 +0100 5646599 http://www.medworm.com/index.php?rid=5646598&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04524.x SummaryBased on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)‐infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV‐infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti‐retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV‐infected patients with CD4+ T cell count <50 cells/µl compared with ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646598 Thu, 02 Feb 2012 11:18:41 +0100 5646598 http://www.medworm.com/index.php?rid=5646597&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04525.x SummaryComplete complement component 6 deficiency (C6Q0) is a co‐dominant genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. Affected individuals have two affected alleles which can be homozygous or compound heterozygous for the particular gene defects they carry. This disorder has been diagnosed relatively frequently in Western Cape South Africans. Affected patients are prescribed penicillin prophylaxis. In 2004 we commenced a clinical follow‐up study of 46 patients. Of these, 43 had family age‐matched C6 sufficient controls. Participants were classified as either (i) well, or (ii) having a serious illness (SI) or died (D). An SI was a long‐term illness that did not allow the performance of normal daily activities. Among 43 patien... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646597 Thu, 02 Feb 2012 11:18:35 +0100 5646597 http://www.medworm.com/index.php?rid=5646596&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04537.x SummaryInterferon (IFN)‐γ is a cytokine with immunomodulatory properties, which has been shown previously to enhance the generation of tolerogenic dendritic cells (DC) when administered early ex vivo in 7‐day monocyte‐derived DC culture. To generate tolerogenic DC rapidly within 48 h, human monocytes were cultured for 24 h with interleukin (IL)‐4 and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) in the presence (IFN‐γ‐DC) or absence of IFN‐γ (500 U/ml) (UT‐DC). DC were matured for 24 h with TNF‐α and prostaglandin E2 (PGE2). DC phenotype, signal transducer and activator of transcription‐6 (STAT‐6) phosphorylation and promotion of CD4+CD25+CD127neg/lowforkhead box P3 (FoxP3)hi T cells were analysed by flow cytometry. DC nuclear factor (NF)... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646596 Thu, 02 Feb 2012 11:18:33 +0100 5646596 http://www.medworm.com/index.php?rid=5646595&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04528.x SummaryThe immune receptor expressed on myeloid cells 1 (IREM‐1/CD300F) has been shown to inhibit various inflammatory processes in myeloid cells, such as macrophages and mast cells. IREM‐1 exerts its inhibitory effect through its intracellular immunoreceptor tyrosine‐based inhibition motifs (ITIMs). In order to generate immunomodulatory molecules that can regulate the inflammatory activation of macrophages, decapeptides representing each of the five ITIM‐like sequences in the cytoplasmic tail of IREM‐1 were synthesized in conjugation with human immunodeficiency virus‐transactivator of transcription (HIV‐TAT48–57), which was added to promote internalization of the peptides. Interestingly, all these TAT–ITIM fusion peptides inhibited Toll‐like receptor (TLR)‐mediated p... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646595 Thu, 02 Feb 2012 11:18:31 +0100 5646595 http://www.medworm.com/index.php?rid=5646594&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04532.x SummaryIn clinical practice it is possible to find patients with clinical signs suggestive of anti‐phospholipid syndrome (APS) who are persistently negative for the routinely used anti‐phospholipid antibodies (aPL). Therefore, the term proposed for these cases was seronegative APS (SN‐APS). We investigated the clinical usefulness of thin‐layer chromatography (TLC) immunostaining in detecting serum aPL in patients presenting clinical features of SN‐APS. Sera from 36 patients with SN‐APS, 19 patients with APS, 18 patients with systemic lupus erythematosus (SLE), 20 anti‐hepatitis C virus (HCV)‐positive subjects and 32 healthy controls were examined for aPL using TLC immunostaining. Anti‐β2‐glycoprotein‐I, anti‐annexin II, anti‐annexin V and anti‐prothrombin antib... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646594 Thu, 02 Feb 2012 11:18:29 +0100 5646594 http://www.medworm.com/index.php?rid=5646593&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04523.x SummaryEnterocytes used to be studied particularly in terms of digestion protagonists. However, as the immune functions of the intestinal tract were better understood, it became clear that enterocytes are not mere bystanders concerning the induction of immune tolerance to dietary peptides and gut microbiota. In fact, enterocytes are involved actively in shaping the intestinal immune environment, designed for maintaining a non‐belligerent state. This tolerant milieu of the gut immune system is achieved by keeping a balance between suppression and stimulation of the inflammatory responses. Our review presents the current state of knowledge concerning the relationship between enterocytes and immune cells (dendritic cells, lymphocytes), with emphasis on the enterocytes' impact on the mechani... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646593 Thu, 02 Feb 2012 11:18:24 +0100 5646593 http://www.medworm.com/index.php?rid=5646592&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04533.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESAllergy, Host Responses, Cancer, Type 1 diabetes and viruses, Metabolic diseases.SummaryThe disease‐based discovery of the molecular basis for autoinflammatory diseases has led not only to a rapidly growing number of clinically and genetically identifiable disorders, but has unmantled key inflammatory pathways such as the potent role of the alarm cytokine interleukin (IL)‐1 in human disease. Following its initial failures in the treatment of sepsis and the moderate success in the treatment of rheumatoid arthritis, IL‐1 blocking therapies had a renaissance in the treatment of a number of autoinflammatory conditions, and IL‐1 blocking therapies have been Food and Drug Administration (FDA)‐approved for the treatmen... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646592 Thu, 02 Feb 2012 11:18:22 +0100 5646592 http://www.medworm.com/index.php?rid=5646591&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04535.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESAllergy, Host Responses, Cancer, Type 1 diabetes and viruses, Metabolic diseases.SummaryAutoinflammatory syndromes are disorders characterized by the hyperactivation of the innate immune system in the absence of microbial infection or autoantibody production. Some autoinflammatory syndromes are associated with recurrent episodes of fever and systemic inflammation that are caused by dysregulated activation of inflammasomes, molecular platforms responsible for the activation of caspase‐1 and the production of interleukin (IL)‐1β. In this review we will discuss the role of IL‐1β and the inflammasomes in host defence and how mutations of two genes, NLRP3 and PYRIN, leads to the autoinflammatory syndromes, cryopyrin‐... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646591 Thu, 02 Feb 2012 11:18:20 +0100 5646591 http://www.medworm.com/index.php?rid=5646590&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04534.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESAllergy, Host Responses, Cancer, Type 1 diabetes and viruses, Metabolic diseases.SummaryInitiation of a successful immune response requires a working set of sensors that detect any noxious agent within the cellular microenvironment and molecular platforms that process this signal to trigger an appropriate effector response. Pattern recognition receptors can engage different signalling cascades that lead to proinflammatory gene expression. At the same time, transcription‐independent events such as activation of proteases and/or phagocytosis are also initiated. The inflammasome pathway constitutes a signalling platform that leads to the activation of so‐called inflammatory caspases, most notably caspase‐1, which plays... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646590 Thu, 02 Feb 2012 11:18:18 +0100 5646590 http://www.medworm.com/index.php?rid=5646588&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04568.x SummarySystemic lupus erythematosus is a polygenic autoimmune disease characterized by the production of antinuclear autoantibodies that lead to subsequent end organ damage. Previous array‐based studies in patients with SLE have shown that high IgG anti‐nuclear autoantibody reactivity was associated with severe renal lupus whereas IgM polyreactivity was associated with less severe disease. To ascertain how different murine lupus strains recapitulate these different autoantibody profiles seen in patients, serum from NZB/NZW F1, MRL/lpr, NZM2410 and BXSB strains were compared using a comprehensive array–based screen. The array results were verified using ELISA assays. Serum from MRL/lpr mice exhibited high levels of IgG antinuclear antibodies (Abs) as well as anti‐glomerular Abs and ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646588 Thu, 02 Feb 2012 11:17:31 +0100 5646588 http://www.medworm.com/index.php?rid=5646589&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04567.x AbstractClinically available anti‐TNF biologics, which inhibit both soluble (sTNF) and transmembrane forms (tmTNF) of TNF, eliminating all TNF signalling, have successfully treated autoimmune diseases including uveitis. These have potentially serious side‐effects such as reactivation of latent Mycobacterium tuberculosis and therefore, more specific inhibition of TNF signalling pathways may maintain clinical efficacy whilst reducing adverse effects. To determine the effects of specific pharmacological inhibition of sTNF on macrophage activation and migration, we used a mouse model of uveitis (experimental autoimmune uveoretinitis; EAU). We show that selective inhibition of sTNF is sufficient to suppress EAU by limiting inflammatory CD11b+ macrophages and CD4+ T cells migration into the ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5646589 Wed, 01 Feb 2012 05:00:00 +0100 5646589 http://www.medworm.com/index.php?rid=5607704&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04566.x SummaryDetermining the past infecting dengue virus (DENV) serotypes has been difficult due to highly cross‐reactive immune responses from previous DENV infections. Determining the correlates of serotype specific immune responses would be crucial in understanding dengue transmission in the community and would also help to determine the correlates of a protective immune responses. Therefore, we set out to define highly conserved, serotype specific regions of the DENVs.Serotype‐specific and highly conserved regions of the four DENV serotypes were identified using BLAST searches and custom perl scripts. Using ex vivo and cultured ELISpot assays we identified serotype specific T cell epitopes within the four DENV serotypes in healthy adult donors from Sri Lanka. We identified T cell respons... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5607704 Fri, 20 Jan 2012 11:18:15 +0100 5607704 http://www.medworm.com/index.php?rid=5596682&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04565.x In this study, the clinical importance of tumor‐infiltrating CD45RO+ memory T cells was investigated in human oesophageal squamous cell carcinoma (OSCC). CD45RO+ T cells were evaluated by immunohistochemistry in primary OSCC tumors from 105 patients. Patients were classified into two groups as CD45RO+hi or CD45RO+lo based on the number of cells positively stained for CD45RO. No significant difference was observed between CD45RO status and several clinicopathological prognostic factors. However, the postoperative overall and disease‐free survivals for patients of CD45RO+hi were significantly better than CD45RO+lo patients. Furthermore, there were significant correlations of CD45RO status in the primary tumor with postoperative lymph node and pulmonary recurrence, suggesting that memory ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5596682 Tue, 17 Jan 2012 11:17:00 +0100 5596682 http://www.medworm.com/index.php?rid=5580546&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04546.x (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580546 Fri, 13 Jan 2012 11:17:54 +0100 5580546 http://www.medworm.com/index.php?rid=5580545&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04498.x This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)‐induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific‐pathogen‐free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms – bleeding, rectal prolapses and colitis‐induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening af... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580545 Fri, 13 Jan 2012 11:17:52 +0100 5580545 http://www.medworm.com/index.php?rid=5580544&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04508.x SummaryThe immunological hallmark of Omenn syndrome (OS) is the expansion and activation of an oligoclonal population of autoreactive T cells. These cells should be controlled rapidly by immunosuppressive agents, such as cyclosporin A (CsA), to avoid tissue infiltration and to improve the general outcome of the patients. Here we studied the clinical and the immune response to CsA in two Omenn patients and also examined the gene expression profile associated with good clinical response to such therapy. T cell receptor diversity was studied in cells obtained from OS patients during CsA therapy. Characterization of gene expression in these cells was carried out by using the TaqMan low‐density array. One patient showed complete resolution of his symptoms after CsA therapy. The other patient ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580544 Fri, 13 Jan 2012 11:17:49 +0100 5580544 http://www.medworm.com/index.php?rid=5580543&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04504.x This study was conducted to document the proportion of CD4+/interleukin (IL)‐17A+‐, CD16+/indoleamine 2, 3‐dioxygenase (IDO+)‐, forkhead box protein P3 (FoxP3+)‐expressing cells, senescent cells (p16INK4α) and the percentage of interstitial fibrosis (IF) in graft biopsies of kidney transplant recipients participating in the BENEFIT (Bristol‐Myers Squibb IM103008) study. CD4+/IL‐17A+, CD16+/IDO+, FoxP3+ and p16INK4α+ cells were evaluated by immunohistochemistry, and the percentage of IF by morphometry on graft biopsies obtained at time 0 (pre‐implantation) and at 12 months post‐transplant. Senescent cells and CD4+/IL‐17A+ cells were increased among graft biopsies in subjects receiving cyclosporin A (CsA) compared to those under belatacept treatment. Meanwhile, CD16+/ID... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580543 Fri, 13 Jan 2012 11:17:47 +0100 5580543 http://www.medworm.com/index.php?rid=5580542&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04520.x In this study, we investigated the role and expression of T helper type 17 (Th17) cells and Th17 cytokines in human tuberculosis. We show that the basal proportion of interferon (IFN)‐γ‐, interleukin (IL)‐17‐ and IL‐22‐expressing CD4+ T cells and IL‐22‐expressing granulocytes in peripheral blood were significantly lower in latently infected healthy individuals and active tuberculosis patients compared to healthy controls. In contrast, CD4+ T cells expressing IL‐17, IL‐22 and IFN‐γ were increased significantly following mycobacterial antigens stimulation in both latent and actively infected patients. Interestingly, proinflammatory IFN‐γ and tumour necrosis factor (TNF)‐α were increased following antigen stimulation in latent infection. Similarly, IL‐1β, IL�... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580542 Fri, 13 Jan 2012 11:17:45 +0100 5580542 http://www.medworm.com/index.php?rid=5580541&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04513.x SummaryHuman cytomegalovirus (CMV) infection is associated with a higher risk of cardiovascular disease in immunocompromised organ transplant patients. It has been linked with the pathogenesis of elevated arterial blood pressure. However, controversy exists as to whether CMV infection is associated with endothelial function, and little is known about its role as a potential risk factor for early atherosclerosis development at a young age. We aimed to discover if CMV antibody titres are associated with early vascular changes (carotid intima‐media thickness, carotid artery distensibility and brachial artery flow‐mediated dilation), blood pressure elevation or other traditional cardiovascular risk factors. CMV antibody titres were measured in 1074 women and 857 men (aged 24–39 years) ta... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580541 Fri, 13 Jan 2012 11:17:44 +0100 5580541 http://www.medworm.com/index.php?rid=5580540&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04496.x SummaryThe immunomodulatory effects of probiotics were assessed following exposure of normal peripheral blood mononuclear cells (PBMC), cord blood cells and the spleen‐derived monocyte/macrophage cell line CRL‐9850 to Lactobacillus acidophilus LAVRI‐A1, Lb. rhamnosus GG, exopolysaccharides (EPS)‐producing Streptococcus thermophilus St1275, Bifidobacteriun longum BL536, B. lactis B94 and Escherichia coli TG1 strains. The production of a panel of pro‐ and anti‐inflammatory cytokines by PBMC following bacterial stimulation was measured, using live, heat‐killed or mock gastrointestinal tract (GIT)‐exposed bacteria, and results show that (i) all bacterial strains investigated induced significant secretion of pro‐ and anti‐inflammatory cytokines from PBMC‐derived monocytes/... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580540 Fri, 13 Jan 2012 11:17:39 +0100 5580540 http://www.medworm.com/index.php?rid=5580539&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04507.x SummaryAbnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multi‐colour flow cytometry (MFC) in a cohort of well‐characterized CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) compared to normal controls (P < 0·0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P = 0·0034). The previously published as... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580539 Fri, 13 Jan 2012 11:17:37 +0100 5580539 http://www.medworm.com/index.php?rid=5580538&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04519.x We examined the inhibitory effects of the amino acids cysteine, histidine and glycine on the induction of NF‐κB activation, expression of CD62E (E‐selectin) and the production of interleukin (IL)‐6 in HCAECs stimulated with tumour necrosis factor (TNF)‐α. Cysteine, histidine and glycine significantly reduced NF‐κB activation and inhibitor κBα (IκBα) degradation in HCAECs stimulated with TNF‐α. Additionally, all the amino acids inhibited the expression of E‐selectin and the production of IL‐6 in HCAECs, and the effects of cysteine were the most significant. Our results show that glycine, histidine and cysteine can inhibit NF‐κB activation, IκBα degradation, CD62E expression and IL‐6 production in HCAECs, suggesting that these amino acids may exhibit anti‐inf... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580538 Fri, 13 Jan 2012 11:17:36 +0100 5580538 http://www.medworm.com/index.php?rid=5580537&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04511.x SummaryInsulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non‐alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin‐deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non‐immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopol... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580537 Fri, 13 Jan 2012 11:17:32 +0100 5580537 http://www.medworm.com/index.php?rid=5580536&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04505.x SummaryIn systemic lupus erythematosus (SLE), the autoantibodies that form immune complexes (ICs) trigger activation of the complement system. This results in the formation of membrane attack complex (MAC) on cell membrane and the soluble terminal complement complex (TCC). Hyperactive T cell responses are hallmark of SLE pathogenesis. How complement activation influences the T cell responses in SLE is not fully understood. We observed that aggregated human γ‐globulin (AHG) bound to a subset of CD4+ T cells in peripheral blood mononuclear cells and this population increased in the SLE patients. Human naive CD4+ T cells, when treated with purified ICs and TCC, triggered recruitment of the FcRγ chain with the membrane receptor and co‐localized with phosphorylated Syk. These events were ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580536 Fri, 13 Jan 2012 11:17:29 +0100 5580536 http://www.medworm.com/index.php?rid=5580535&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04510.x SummaryUp‐regulation of interleukin (IL)‐17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL‐17 immunity in different stages of CD, including transglutaminase antibody (TGA)‐positive children with potential CD, children with untreated and gluten‐free diet‐treated CD and in children with T1D. Immunohistochemistry was used for identification of IL‐17 and forkhead box protein 3 (FoxP3)‐positive cells and quantitative polymerase chain reaction (qPCR) for IL‐17, FoxP3, retinoic acid‐related orphan receptor (ROR)c and interferon (IFN)‐γ transcripts. IL‐1β, IL‐6 and IL‐17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl‐2 wa... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580535 Fri, 13 Jan 2012 11:17:28 +0100 5580535 http://www.medworm.com/index.php?rid=5580534&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04517.x SummaryOTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESMetabolic Diseases, Host Responses, Allergies, Autoinflammatory Diseases, Type 1 diabetes and viruses.Cancer is one of the most important pathological conditions facing mankind in the 21st century, and is likely to become the most important cause of death as improvements continue in health, diet and life expectancy. The immune response is responsible for controlling nascent cancer through immunosurveillance. If tumours escape this control, they can develop into clinical cancer. Although surgery and chemo‐ or radiotherapy have improved survival rates significantly, there is a drive to reharness immune responses to treat disease. As T cells are one of the key immune cells in controlling cancer, research is under wa... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580534 Fri, 13 Jan 2012 11:17:26 +0100 5580534 http://www.medworm.com/index.php?rid=5580533&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04516.x SummaryOTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESMetabolic Diseases, Host Responses, Allergies, Autoinflammatory Diseases, Type 1 diabetes and viruses.Research into aberrant glycosylation and over‐expression of glycolipids on the surface of the majority of cancers, coupled with a knowledge of glycolipids as functional molecules involved in a number of cellular physiological pathways, has provided a novel area of targets for cancer immunotherapy. This has resulted in the development of a number of vaccines and monoclonal antibodies that are showing promising results in recent clinical trials. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580533 Fri, 13 Jan 2012 11:17:25 +0100 5580533 http://www.medworm.com/index.php?rid=5580532&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04515.x SummaryOTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESMetabolic Diseases, Host Responses, Allergies, Autoinflammatory Diseases, Type 1 diabetes and viruses.Mononuclear phagocytes are cells of the innate immunity that defend the host against harmful pathogens and heal tissues after injury. Contrary to expectations, in malignancies, tumour‐associated macrophages (TAM) promote disease progression by supporting cancer cell survival, proliferation and invasion. TAM and related myeloid cells [Tie2+ monocytes and myeloid‐derived suppressor cells (MDSC)] also promote tumour angiogenesis and suppress adaptive immune responses. These divergent biological activities are mediated by macrophages/myeloid cells with distinct functional polarization, which are ultimately dictated... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580532 Fri, 13 Jan 2012 11:17:23 +0100 5580532 http://www.medworm.com/index.php?rid=5580531&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04514.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESMetabolic Diseases, Host Responses, Allergies, Autoinflammatory Diseases, Type 1 diabetes and viruses.SummaryDespite complex genomic and epigenetic abnormalities, many cancers are irrevocably dependent on an initiating oncogenic lesion whose restoration to a normal physiological activation can elicit a dramatic and sudden reversal of their neoplastic properties. This phenomenon of the reversal of tumorigenesis has been described as oncogene addiction. Oncogene addiction had been thought to occur largely through tumour cell‐autonomous mechanisms such as proliferative arrest, apoptosis, differentiation and cellular senescence. However, the immune system plays an integral role in almost every aspect of tumorigenesis, inclu... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580531 Fri, 13 Jan 2012 11:17:22 +0100 5580531 http://www.medworm.com/index.php?rid=5580528&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04563.x In conclusion, we found that L‐type Ca2+ channel blocker and subtherapeutic dose of cyclosporine act additively to suppress Ca2+‐calcineurin‐NFAT signaling pathway leading to inhibition of T‐cell activities. We purpose that this combination may become a potential treatment of RA. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580528 Fri, 13 Jan 2012 11:16:14 +0100 5580528 http://www.medworm.com/index.php?rid=5580530&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04561.x (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580530 Thu, 12 Jan 2012 05:00:00 +0100 5580530 http://www.medworm.com/index.php?rid=5580529&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04564.x SummaryStatins are 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors of cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on cellular signaling and cellular functions involved in inflammation. Recent reports demonstrated that prior statin therapy reduced the risk of pneumonia or increased survival in patients with community‐acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)‐stimulated human bronchial epithelial cells (BEAS‐2B). Interleukin (IL)‐6 and IL‐8 mRNA expression and protein secretion in LPS‐stimulated cells were significantly inhibited by the lipophilic statin pitavast... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5580529 Thu, 12 Jan 2012 05:00:00 +0100 5580529 http://www.medworm.com/index.php?rid=5571731&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04560.x SUMMARYTolerance to lipopolysaccharide (LPS) constitutes a stress adaptation, in which a primary contact with LPS results in a minimal response when a second exposure with the same stimulus occurs. However, during the tolerant state, active important defense mechanisms are mounted. Our aim was to assess the contribution of neutrophils (PMN) in the clearance of bacterial infection in a mouse model of tolerance to LPS. After tolerance was developed, we investigated in vivo different mechanisms of bacterial clearance. The elimination of a locally induced polymicrobial challenge was more efficient in tolerant mice both in the presence or absence of local macrophages. This was related to a higher number of PMN migrating to the infectious site, as a result of an increased number of PMN from the ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5571731 Thu, 05 Jan 2012 05:00:00 +0100 5571731 http://www.medworm.com/index.php?rid=5571730&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2012.04562.x AbstractPulmonary oedema is a hallmark of acute lung injury (ALI), consisting of various degrees of water and proteins. Physiologically, sodium enters through apical sodium channels (ENaC) and is extruded basolaterally by a sodium‐potassium‐adenosine‐triphosphatase pump (Na+/K+‐ATPase). Water follows to maintain isoosmolar conditions and to keep alveoli dry. We postulated that the volatile anesthetic sevoflurane would positively impact oedema resolution in an in vitro and in vivo model of ALI.Alveolar epithelial type II cells (AECII) and mixed alveolar epithelial cells (mAEC) were stimulated with 20 µg/ml lipopolysaccharides (LPS) and co‐exposed to sevoflurane for 8 hours. In vitro active sodium transport via ENaC and Na+/K+‐ATPase was determined, assessing 22sodium and 86rubi... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5571730 Sun, 01 Jan 2012 05:00:00 +0100 5571730 http://www.medworm.com/index.php?rid=5551782&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04551.x AbstractSeveral assays to measure pre‐existing allospecific T cell immunity in renal transplant candidates have been developed in the past years. In 46 patients, we used flowcytometry based mixed lymphocyte culture, to measure the precursor frequency and phenotype of alloreactive T cells before renal transplantation, using donorspecific or 3rd party cells for allostimulation. Allostimulation induced upregulation of costimulatory molecules, chemokine receptors relevant for migration of T cells into the graft, and effector proteins. Recipients prone for acute rejection had a higher precursor frequency of alloreactive CD8+ T cells and a lower percentage of IL‐7Rα expressing alloreactive CD8+ T cells than non‐rejectors. These data point to quantitative and qualitative differences betwee... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551782 Fri, 30 Dec 2011 23:49:59 +0100 5551782 http://www.medworm.com/index.php?rid=5551783&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04550.x Conclusion:  Prevaccination IgG subclass levels did not correlate with the ability to develop robust antibody responses to the 2009 influenza A (H1N1) monovalent vaccine. IgG2 deficiencies were common among HIV‐infected persons but did not correlate with poor influenza vaccine responses. Further investigations into the etiology of disparate vaccine responses are needed. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551783 Thu, 29 Dec 2011 05:00:00 +0100 5551783 http://www.medworm.com/index.php?rid=5551793&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04552.x This study describes a novel innate defense mechanism adopted by NK cells to control M. tb infection. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551793 Wed, 28 Dec 2011 05:00:00 +0100 5551793 http://www.medworm.com/index.php?rid=5551792&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04553.x (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551792 Wed, 28 Dec 2011 05:00:00 +0100 5551792 http://www.medworm.com/index.php?rid=5551791&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04554.x AbstractConvincing evidence now indicates that viruses are associated with type 1 diabetes (T1D) development and progression. Human enteroviruses (HEV) have emerged as prime suspects based on detection frequencies around clinical onset in patients and their ability to rapidly trigger hyperglycemia in the NOD mouse. Whether or not HEV can truly cause islet autoimmunity or rather act by accelerating ongoing insulitis remains a matter of debate. In view of the disease's globally rising incidence it is hypothesized that improved hygiene standards may reduce the immune system's ability to appropriately respond to viral infections. Arguments in favor and against viral infections as major etiological factors in T1D will be discussed in conjunction with potential pathological scenarios. More profo... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551791 Wed, 28 Dec 2011 05:00:00 +0100 5551791 http://www.medworm.com/index.php?rid=5551790&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04555.x AbstractThe hypothesis that enteroviral infections under some circumstances can lead to type 1 diabetes was proposed several decades ago, based initially on evidence from animal studies and seroepidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we critically review recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, perhaps partially due to heterogeneity in study design and a limited number of subjects studied. An... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551790 Wed, 28 Dec 2011 05:00:00 +0100 5551790 http://www.medworm.com/index.php?rid=5551788&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04556.x (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551788 Wed, 28 Dec 2011 05:00:00 +0100 5551788 http://www.medworm.com/index.php?rid=5551787&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04557.x Summary (Abstract)Type 1 diabetes (T1D) is an autoimmune disease arising as a consequence of a misdirected T cell response to the pancreatic beta cell. In recent years, there has been a growing interest in the innate immune system as a regulator of disease development. Genome wide association studies have identified diabetes‐associated polymorphisms in genes encoding proteins with functions related to the innate immune response. Moreover, enteroviruses, known to activate a strong innate immune response, have been implicated in the disease pathogenesis. In this review, we discuss the innate immune response elicited by enteroviruses and how this response may regulate T1D development. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551787 Wed, 28 Dec 2011 05:00:00 +0100 5551787 http://www.medworm.com/index.php?rid=5551786&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04558.x SummaryThymus dysfunction, especially immune suppression, is frequently associated with various virus infections. Whether viruses may disturb the thymus function and play a role in the pathogenesis of autoimmune diseases is an opened issue. Enteroviruses, especially Coxsackievirus B4 (CV‐B4), have been largely involved suggested as potential inducers or aggravating factors of T1D pathogenesis in genetically predisposed individuals. Several pathogenic mechanisms of enterovirus‐induced T1D have been suggested. One of these mechanisms is the impairment of central self‐tolerance due to viral infections. Coxsackievirus‐B4 is able to infect murine thymus in‐vitro and in vivo and to infect human thymus in vitro. Thymic epithelial cells and thymocytes are target of infection with this vi... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551786 Wed, 28 Dec 2011 05:00:00 +0100 5551786 http://www.medworm.com/index.php?rid=5551784&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04559.x SummaryType 1 diabetes results from an interaction between genetic and environmental factors. Coxsackieviruses B (CV‐B) are major environmental candidates as suggested by epidemiological and experimental studies. The mechanisms leading to the disease involve interactions between the virus, host target tissue (pancreas) and the immune system. The infection of target cells with viruses can be prevented by antibodies. At the opposite the infection can be enhanced by antibodies. The antibody‐dependent enhancement (ADE) of infection has been described with various viruses, especially Picornaviruses. In mice infected with CV‐B3 this phenomenon resulted in an extended inflammatory reaction and myocarditis. In the human system non neutralizing antibodies can increase the infection of monocyt... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5551784 Wed, 28 Dec 2011 05:00:00 +0100 5551784 http://www.medworm.com/index.php?rid=5523710&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04549.x This study aimed to investigate the effects of MS, particularly cyclic strain, on immune response genes, as well as SIRT1 and its signal transduction pathways, in human PDL cells. MS upregulated the expression of SIRT1 and immune response genes encoding cytokines (TNF‐α, IL‐1β), chemokines (IL‐8, CCL‐20), defensins (hBD‐2, hBD‐3), and Toll‐like receptors (TLR‐2 and TLR‐4) in a force‐ and time‐dependent manner. The SIRT1 inducers resveratrol and isonicotinamide attenuated MS‐induced cytokine and chemokine expression, but enhanced the expression of defensins and TLRs. Blockade of SIRT1 activity by the SIRT1 inhibitors sirtinol and nicotinamide, and downregulation of SIRT1 expression by SIRT1 siRNA, reduced the stimulatory effects of MS on defensins and TLRs, but inc... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5523710 Wed, 21 Dec 2011 23:50:07 +0100 5523710 http://www.medworm.com/index.php?rid=5523711&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04548.x Conclusion: The present results demonstrate that IL‐1R1 is induced following extravasation and exists on the neutrophil surface, as well as in a mobile intracellular pool. Furthermore, neutrophils express functional IL‐1R1 as demonstrated by the induction of chemokines following IL‐1 stimulation. The results indicate a potential role for IL‐1 in the activation of neutrophils at inflammatory sites. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5523711 Tue, 20 Dec 2011 05:00:00 +0100 5523711 http://www.medworm.com/index.php?rid=5504100&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04547.x AbstractPlasma exchange is increasingly used as an individual therapeutic decision for treating of severe, steroid resistant relapses of Multiple Sclerosis (MS). However, given that its mechanism of action in this CD4+T cell mediated autoimmune disease remained unknown, it's not yet considered as a routine therapy for this prevalent neuroimmune disorder. In this regard, we hypothesized that plasma exchange, by depleting the body of inflammatory mediators that acts as providers of co‐stimulatory signals for the adaptive immune system, provides the immune system an exceptional break for de novo recognizing of auto‐antigens in a tolerogenic manner. This may lead to an increase in the frequency and function of myelin specific regulatory T cells. For evaluating this we suggest some invitro ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5504100 Thu, 15 Dec 2011 23:49:50 +0100 5504100 http://www.medworm.com/index.php?rid=5486178&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04545.x This study shows that IFNγ, a dominant cytokine in intestinal mucosa in active CD, is the most potent inducer of TG2, and synergism with TNFα may contribute to exacerbate the pathogenic mechanism of CD. Selective inhibition of signalling pathways may be of therapeutic benefit. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5486178 Fri, 09 Dec 2011 23:50:20 +0100 5486178 http://www.medworm.com/index.php?rid=5486179&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04543.x SummaryExcessive Th1 cell activity has been reported in Behcet's disease (BD). Recently, association of Th17 cells with certain autoimmune diseases was reported, and we thus investigated circulating Th17 cells in BD.CD4+ CD45RO‐ (naïve) T cells were cultured with Th0, Th1, Th2 and Th17 related cytokines and antibodies, and their mRNA was studied by real‐time PCR. When naïve CD4+ T cells were cultured with Th1 and Th17 related cytokines, interferon (IFN)γ mRNA and interleukin (IL)‐17 mRNA were up‐regulated respectively in BD patients. Naïve CD4+ T cells cultured in a Th17 cell inducing condition expressed IL‐23 receptor (IL‐23R) mRNA excessively. IL‐17 mRNA expression was induced only when naïve CD4+ T cells were cultured in the presence of IL‐23. CD4+ T cells cultured ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5486179 Fri, 09 Dec 2011 05:00:00 +0100 5486179 http://www.medworm.com/index.php?rid=5486180&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04544.x AbstractDeath rules our lives. In this short review, we summarise new insights into molecular mechanisms of neurodegeneration. Here we review the most important processes of cell death: apoptosis and oncosis. We focus on autophagy, which is pivotal for neuronal homeostasis, in the context of neurodegeneration, infection and immunity. Its dysfunction has been linked to several neurodegenerative diseases such as Parkinson's, Huntington's and Alzheimer diseases. Our understanding is still incomplete but may highlight attractive new avenues for the development of treatment strategies to combat neurodegenerative diseases. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5486180 Wed, 07 Dec 2011 05:00:00 +0100 5486180 http://www.medworm.com/index.php?rid=5475916&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04542.x AbstractIn order to build a common data pool and estimate the disease burden of primary immunodeficiencies (PID) in Europe, the European Society for Immunodeficiencies (ESID) has developed an internet‐based database for clinical and research data on patients with PID. This database is a platform for epidemiologic analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease‐associated genes.Since its start in 2004, 13,708 patients from 41 countries have been documented in the ESID Database. Common variable immunodeficiency (CVID) represents the most common entity with 2,880 patients or 21% of all entries, followed by selective immunoglobulin A (sIgA) deficiency (1424 patients, 10.4%). The total documented prevalence of PID is h... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5475916 Tue, 06 Dec 2011 23:51:10 +0100 5475916 http://www.medworm.com/index.php?rid=5475917&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04541.x In conclusion, our results support the involvement of coagulation and fibrinolysis in pathophysiology of HAE and show possible application of simultaneous measurement of thrombin and plasmin generation to evaluate different clinical conditions in HAE patients. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5475917 Mon, 05 Dec 2011 05:00:00 +0100 5475917 http://www.medworm.com/index.php?rid=5468219&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04487.x SummaryReperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia–reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty‐four hours after transplant, the kidney ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468219 Sat, 03 Dec 2011 23:52:08 +0100 5468219 http://www.medworm.com/index.php?rid=5468218&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04486.x In this study, we defined the role for the shift in immunodominant epitopes of Col‐V in inducing T helper phenotype switch leading to immunity to Col‐V and BOS. Sera and lavage from BOS+ LTx recipients with antibodies to Col‐V were analysed. Two years prior to BOS, patients developed antibodies to both Col‐V,α1(V) and α2(V) chains. However, at clinical diagnosis of BOS, antibodies became restricted to α1(V). Further, lung biopsy from BOS(+) patients bound to antibodies to α1(V), indicating that these epitopes are exposed. Fourteen Col‐V peptides [pep1–14, pep1–4 specific to α1(V), pep5–8 to α1,2(V) and pep9–14 to α2(V)] which bind to HLA‐DR4 and ‐DR7, demonstrated that prior to BOS, pep 6, 7, 9, 11 and 14 were immunodominant and induced interleukin (IL)‐10. H... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468218 Sat, 03 Dec 2011 23:52:06 +0100 5468218 http://www.medworm.com/index.php?rid=5468217&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04488.x SummaryThe ready access to commercially available multiplex assays and the importance of inflammation in disease pathogenesis has resulted in an abundance of studies aimed at identifying surrogate biomarkers for different clinically important questions. Establishing a link between a biomarker and disease pathogenesis, however, is quite complex, and in some instances this complexity is compounded by post‐translational modifications and the use of immunoassays that do not always discriminate between the different forms of the same protein. Herein, we provide a detailed description of an assay system that has been established to discriminate the agonist form of CXCL10 from the NH2‐terminal truncated form of the molecule generated by dipeptidylpeptidase IV (DPP4) cleavage. We demonstrate t... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468217 Sat, 03 Dec 2011 23:52:03 +0100 5468217 http://www.medworm.com/index.php?rid=5468216&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04485.x SummaryThe disturbed cytokine–chemokine network could play an important role in the onset of diseases with inflammatory processes such as chronic idiopathic urticaria (CIU). Our main objectives were to evaluate the relation between proinflammatory chemokine serum levels from CIU patients and their response to autologous skin test (ASST) and basophil histamine release (BHR). We also aimed to assess the chemokine secretion by peripheral blood mononuclear cells (PBMC) upon polyclonal stimulus and to evaluate chemokine C–C ligand 2/C‐X‐C chemokine 8 (CCL2/CXCL8) and Toll‐like receptor‐4 (TLR‐4) expression in monocytes. We observed significantly higher serum levels of the CXCL8, CXCL9, CXCL10 and CCL2 in CIU patients compared to the healthy group, regardless of the BHR or ASST res... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468216 Sat, 03 Dec 2011 23:52:01 +0100 5468216 http://www.medworm.com/index.php?rid=5468215&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04492.x SummaryImmune dysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) is a rare syndrome due to a mutation in the forkhead box protein 3 gene (FOXP3) leading to an impaired regulatory T cell (Treg) activity associated both with skewed T helper type 2 (Th2) response and autoreactive phenomena. The purpose of this study was to describe a combined proteomics and genomics approach to comprehensively evaluate clinical and immunological phenotypes of patients affected by IPEX. T cell receptor (TCR)‐Vβ repertoire and peripheral blood lymphocytes phenotype from three brothers affected by IPEX were studied by flow cytometry. Specific immunoglobulin (Ig)E were evaluated by means of an allergenic molecules microarray [immuno solid‐phase allergen chip (ISAC)]. Total RNA was extracted an... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468215 Sat, 03 Dec 2011 23:51:59 +0100 5468215 http://www.medworm.com/index.php?rid=5468214&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04494.x In conclusion, the decreased Nck1 protein in Jurkat T cells resulted in an impairment of TCR–CD3‐mediated activation involving a defective Erk phosphorylation pathway. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468214 Sat, 03 Dec 2011 23:51:55 +0100 5468214 http://www.medworm.com/index.php?rid=5468213&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04493.x SummaryDysregulations concerning the composition and function of regulatory T cells (Tregs) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six‐colour flow cytometric analysis to demonstrate that the total CD4+CD127low+/−CD25+forkhead box protein 3 (FoxP3)+ Treg cell pool contains four distinct Treg subsets: DRhigh+CD45RA‐, DRlow+CD45RA‐, DR‐CD45RA‐ Tregs and naive DR‐CD45RA+ Tregs. During the normal course of pregnancy, the most prominent changes in the composition of the total Treg cell pool were observed between the 10th and 20th weeks of gestation, with a clear decrease in the percentage of DRhigh+CD45RA‐ and DRlow+CD45RA‐ Tregs and a clear increase in the percentage of naive DR‐CD45RA+ Tregs. After that time, the composition of... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468213 Sat, 03 Dec 2011 23:51:53 +0100 5468213 http://www.medworm.com/index.php?rid=5468212&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04489.x In this study, in order to generate a potent anti‐tumour immune response against RCC, we produced recombinant CA9‐Acinetobacter baumannii outer membrane protein A (AbOmpA) fusion proteins, designated CA9‐AbOmpA, and investigated the ability of DCs pulsed with CA9‐AbOmpA fusion proteins in a murine renal cell carcinoma (RENCA) model. A recombinant CA9‐AbOmpA fusion protein was composed of a unique proteoglycan‐related region of CA9 (1–120 amino acids) fused at the C‐terminus with transmembrane domain of AbOmpA (1–200 amino acids). This fusion protein was capable of inducing DC maturation and interleukin (IL)‐12 production in DCs. Interaction of DCs pulsed with CA9‐AbOmpA fusion proteins with naive T cells stimulated secretion of IL‐2, interferon (IFN)‐γ and tumour... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468212 Sat, 03 Dec 2011 23:51:51 +0100 5468212 http://www.medworm.com/index.php?rid=5468211&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04495.x SummaryDevelopment of high‐risk combinations of multiple islet autoantibodies and type 1 diabetes is associated with high‐affinity insulin autoantibodies (IAA), but IAA affinity measurements require large serum volumes. We therefore investigated whether a simplified method of IAA affinity measurement using a low concentration of unlabelled insulin (ULI) competitor discriminated between moderate–high‐ and low‐affinity IAA and identified individuals at highest risk of disease. Samples were assayed by radiobinding microassay using high (4·0 × 10−5 mol/l) and low (7 × 10−9 mol/l) ULI concentrations for competitive displacement in three cohorts of IAA‐positive individuals; (1) 68 patients with newly‐diagnosed type 1 diabetes; (2) 40 healthy schoolchildren; and (... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468211 Sat, 03 Dec 2011 23:51:49 +0100 5468211 http://www.medworm.com/index.php?rid=5468210&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04503.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESMetabolic Diseases, Host Responses, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses.SummaryAllergen‐specific immunotherapy is an effective clinical treatment for hypersensitivity to many allergens. Studies of basophils during immunotherapy have provided insight into underlying immune mechanisms and support the potential use of basophil activation as a biomarker of clinical outcomes. This review examines the evidence for different pathways of basophil modulation associated with various forms of immunotherapy. Better understanding the molecular mechanisms of basophil activation and desensitization and the relationship between suppression of these effector cells to clinical outcomes holds promise for further... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468210 Sat, 03 Dec 2011 23:51:48 +0100 5468210 http://www.medworm.com/index.php?rid=5468209&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04502.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESAllergy, Metabolic Diseases, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses.SummaryHerpes virus infections are chronic and co‐exist with acquired immune responses that generally prevent severe damage to the host, while allowing periodic shedding of virus and maintenance of its transmission in the community. Herpes simplex viruses type 1 and 2 (HSV‐1, HSV‐2) are typical in this regard and are representative of the viral subfamily Alphaherpesvirinae, which has a tropism for neuronal and epithelial cells. This review will emphasize recent progress in decoding the physiologically important CD8+ and CD4+ T cell responses to HSV in humans. The expanding data set is discussed in the context of the search fo... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468209 Sat, 03 Dec 2011 23:51:46 +0100 5468209 http://www.medworm.com/index.php?rid=5468208&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04501.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESAllergy, Host Responses, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses.SummaryHistorically, the development of type 2 diabetes has been considered not to have an autoimmune component, in contrast to the autoimmune pathogenesis of type 1 diabetes. In this review we will discuss the accumulating data supporting the concept that islet autoreactivity and inflammation is present in type 2 diabetes pathogenesis, and the islet autoimmunity appears to be one of the factors associated with the progressive nature of the type 2 diabetes disease process. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468208 Sat, 03 Dec 2011 23:51:44 +0100 5468208 http://www.medworm.com/index.php?rid=5468207&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04500.x OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESAllergy, Metabolic Diseases, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses.SummaryInvariant natural killer T (iNKT) cells have been shown to play a key role in the regulation of immunity in health and disease. However, iNKT cell responses have also been found to influence both rejection and the induction of tolerance following transplantation of allogeneic cells or organs. Although a number of mechanisms have been identified that lead to iNKT cell activation, how iNKT cells are activated following transplantation remains unknown. This review will attempt to identify potential mechanisms of iNKT cell activation in the context of transplantation by applying knowledge garnered from other disease situations. ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468207 Sat, 03 Dec 2011 23:51:43 +0100 5468207 http://www.medworm.com/index.php?rid=5468206&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04499.x SummaryOTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIESMetabolic Diseases, Host Responses, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses.There is no approved therapy for food allergy. The current standard of care is elimination of the triggering food from the diet and accessibility to epinephrine. Immunotherapy is a promising treatment approach. While desensitization to most foods seems feasible, it remains unclear if a permanent state of tolerance is achievable. The research team at Duke is pioneering immunotherapy for food allergies. Work here has evolved over time from small open‐label pilot studies to larger randomized designs. Our data show that immunological changes associated with immunotherapy include reduction in mast cell reactivity, decrea... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468206 Sat, 03 Dec 2011 23:51:41 +0100 5468206 http://www.medworm.com/index.php?rid=5468205&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04469.x We describe how these studies have aided the identification of subsets of transitional B cells and also a robust memory B cell phenotype. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468205 Sat, 03 Dec 2011 23:51:39 +0100 5468205 http://www.medworm.com/index.php?rid=5468204&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04460.x SummaryOTHER ARTICLES PUBLISHED IN THIS MINI‐REVIEW SERIES ON B CELL SUBSETS IN DISEASEB cells in multiple sclerosis: drivers of disease pathogenesis and Trojan horse for Epstein—Barr virus entry to the central nervous system? Clinical and Experimental Immunology 2012, 167: 1–6. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes. Clinical and Experimental Immunology 2012, 167: 15–25.Systemic lupus erythematosus (SLE) and Sjögren's syndrome are autoimmune disorders which are characterized by a disturbed B cell homeostasis which leads ultimately to dysfunction of various organs. One of the B cell subsets that appear in abnormal numbers is the population of transitional B cells, which is increased in th... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468204 Sat, 03 Dec 2011 23:51:37 +0100 5468204 http://www.medworm.com/index.php?rid=5468203&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04446.x SummaryOTHER ARTICLES PUBLISHED IN THIS MINI‐REVIEW SERIES ON B CELL SUBSETS IN DISEASETransitional B cells in systemic lupus erythematosus and Sjögren's syndrome: clinical implications and effects of B cell‐targeted therapies. Clinical and Experimental Immunology 2012, 167: 7–14. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes. Clinical and Experimental Immunology 2012, 167: 15–25.The recent success of therapies directed at B cells has highlighted their potential as central players in multiple sclerosis (MS) pathogenesis. Exciting new data showed that B cell depletion led to reduced clinical and magnetic resonance imaging (MRI) evidence of disease activity. However, the mechanisms of action remai... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468203 Sat, 03 Dec 2011 23:51:35 +0100 5468203 http://www.medworm.com/index.php?rid=5468199&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04540.x ABSTRACTBone marrow‐derived mesenchymal stromal cells (BM‐MSCs) have immunosuppressive properties and have been used to treat steroid‐refractory acute graft‐versus‐host disease (GVHD) in stem cell transplant patients. Cells with similar capacities can also be found in term placental tissue. We have isolated stromal cells from term fetal membrane (FMSCs), umbilical cords (UCSCs), and placental villi (PVSCs) as well as from bone marrow and compared their immunoregulatory capacity in allogeneic settings. We found that FMSCs and UCSCs significantly suppressed proliferation in mixed lymphocyte reactions (MLRs), whereas PVSCs showed inconsistent suppressive effects. When added to MLR cultures, FMSCs suppressed the production of IFN‐γ and IL‐17, whereas UCSCs and PVSCs promoted the... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5468199 Sat, 03 Dec 2011 23:50:24 +0100 5468199 http://www.medworm.com/index.php?rid=5456558&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04537.x AbstractInterferon‐γ (IFNγ) is a cytokine with immunomodulatory properties, which has previously been shown to enhance the generation of tolerogenic dendritic cells (DC) when administered early ex‐vivo in 7 day monocyte‐derived DC culture. To rapidly generate tolerogenic DC within 48h, human monocytes were cultured for 24h with IL‐4 and GMCSF in the presence (IFNγ‐DC) or absence of IFN‐γ (500U/ml) (UT‐DC). DC were matured for 24h with TNF‐α and PGE2. DC phenotype, STAT‐6 phosphorylation and promotion of CD4+CD25+CD127NEG/LOWFoxP3HI T‐cells were analysed by flow‐cytometry. DC NF‐κB transcription factor RELB and IL‐12p70 protein expression were also determined. Phenotypically IFNγ‐DC displayed reduced DC maturation marker CD83 by 62% and costimulation molec... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5456558 Wed, 30 Nov 2011 23:50:23 +0100 5456558 http://www.medworm.com/index.php?rid=5456560&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04539.x In this study, we demonstrate that engagement of another co‐stimulatory receptor on both LPT and PBT, namely CD28, by a single mAb, respectively, strongly activates the former but not the latter through a PI3‐kinase dependent signaling pathway leading to the production of inflammatory cytokines such as IL‐2, TNF‐α, IFN‐γ, and GM‐CSF.In addition to the high sensitivity of LPT to CD2 stimulation this finding supports the notion that “non‐specific/innate” mechanisms to activate T‐lymphocytes play a predominant role vis à vis “TCR driven/adaptive” responses in the intestinal mucosa. Furthermore, it suggests that results from pre‐clinical tests for therapeutic antibodies performed with human blood derived T cells are likely insufficient to predict reactivities of ti... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5456560 Mon, 28 Nov 2011 05:00:00 +0100 5456560 http://www.medworm.com/index.php?rid=5456559&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04538.x AbstractSeveral studies correlated genetic background and pancreatic islet‐cell autoantibody status (type and number) in type 1 A diabetes mellitus (T1AD) but there are no data evaluating the relationship among these markers with serum cytokines, T regulatory cells and β‐cell function. This characterization has a potential importance to T1AD patients’ stratification and follow‐up in therapeutics prevention. Here we showed that peripheral sera cytokines (IL‐12, 1L‐6, IL‐1β, TNFα, IL‐10) and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (p < 0.001) (Table 1). Among T1AD, we found a positive correlation between CXCL‐10 and CCL‐2 (rs = 0.80; p = 0.000), IL‐8 and TNFα (rs... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5456559 Mon, 28 Nov 2011 05:00:00 +0100 5456559 http://www.medworm.com/index.php?rid=5449417&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04535.x AbstractAutoinflammatory syndromes are disorders characterized by the hyperactivation of the innate immune system in the absence of microbial infection or autoantibody production. Some autoinflammatory syndromes are associated with recurrent episodes of fever and systemic inflammation that are caused by dysregulated activation of inflammasomes, molecular platforms responsible for the activation of caspase‐1 and the production of IL‐1β. In this review we will discuss the role of IL‐1β and the inflammasomes in host defense and how mutations of two genes, NLRP3 and PYRIN, leads to the autoinflammatory syndromes, Cryopyrin‐Associated Periodic Syndromes (CAPS) and Familial Mediterranean Fever (FMF). Both CAPS and FMF are characterized by increased inflammasome activity and overproduct... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5449417 Sun, 27 Nov 2011 23:51:17 +0100 5449417 http://www.medworm.com/index.php?rid=5449422&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04533.x AbstractThe disease based discovery of the molecular basis for autoinflammatory diseases has not only led to a rapidly growing number of clinically and genetically identifiable disorders but has unmantled key inflammatory pathways such as the potent role of the alarm cytokine interleukin‐1 (IL‐1) in human disease. Following its initial failures in the treatment of sepsis and the moderate success in the treatment of rheumatoid arthritis, IL‐1 blocking therapies had a renaissance in the treatment of a number of autoinflammatory conditions and IL‐1 blocking therapies have been FDA approved for the treatment of the autoinflammatory conditions; cryopyrin associated periodic syndromes (CAPS). CAPS and deficiency of the IL‐1 receptor antagonist (DIRA), both genetic conditions with molec... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5449422 Fri, 25 Nov 2011 05:00:00 +0100 5449422 http://www.medworm.com/index.php?rid=5449421&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04534.x SummaryInitiation of a successful immune response requires a working set of sensors that detect any noxious agent within the cellular microenvironment and molecular platforms that process this signal to trigger an appropriate effector response. Pattern recognition receptors can engage different signaling cascades that lead to proinflammatory gene expression. At the same time transcription‐independent events like activation of proteases and/or phagocytosis are also initiated. The inflammasome pathway constitutes a signaling platform that leads to the activation of so‐called inflammatory caspases, most notably caspase‐1, which plays a pivotal role in the cleavage and thus maturation of proinflammatory cytokines, but also in the induction of pyroptosis, a special type of cell death. In ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5449421 Fri, 25 Nov 2011 05:00:00 +0100 5449421 http://www.medworm.com/index.php?rid=5449419&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04536.x ABSTRACTLeishmaniasis is a group of important parasitic diseases affecting millions worldwide. To better understand the quality of T helper 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg), in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total gamma interferon (IFN‐γ) producing CD4+T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunc... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5449419 Fri, 25 Nov 2011 05:00:00 +0100 5449419 http://www.medworm.com/index.php?rid=5440075&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04532.x ABSTRACTIn clinical practice it is possible to find patients with clinical signs suggestive of antiphospholipid syndrome (APS) who are persistently negative for the routinely used antiphospholipid antibodies (aPL). Therefore, it was proposed for these cases the term of seronegative APS (SN‐APS).We investigated the clinical usefulness of thin layer chromatography (TLC) immunostaining in detecting serum aPL in patients presenting clinical features of SN‐APS.Sera from 36 patients with SN‐APS, 19 patients with APS, 18 patients with systemic lupus erythematosus (SLE), 20 anti‐HCV positive subjects and 32 healthy controls were examined for aPL using TLC immunostaining. Anti‐β2‐glycoprotein‐I, anti‐annexin II, anti‐annexin V and anti‐prothrombin antibodies were tested by enzy... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5440075 Thu, 24 Nov 2011 23:51:27 +0100 5440075 http://www.medworm.com/index.php?rid=5440076&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04531.x AbstractDespite recent tissue‐engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunoflurescence targeted at immunologically relevant molecules, we have studied the early (48 h. and one week) immunological responses within larynxes transplantated between 7 pairs of NIH minipigs fully homozygous at the MHC locus.There were only small changes in expression of some molecules (relative to inter‐individual variation) and these were clearest in samples from the sub‐glottic region, where the areas of co‐expression of CD25+CD45RC‐CD8‐ and of CD163+CD172+MHCII‐ increased at one week after transplant.In one case, infiltration by recipient T‐cells... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5440076 Wed, 23 Nov 2011 05:00:00 +0100 5440076 http://www.medworm.com/index.php?rid=5431044&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04530.x This study was performed to clarify the mechanism of elastic fiber deposition in the peripheral portal tracts of IPH liver in relation to serum anti‐endothelial cell antibodies (AECA). In vitro experiments were performed using human dermal microvascular endothelial cells (HMVEC) and patients’ sera. The presence of serum AECA was assayed by a cell‐based ELISA using HMVEC. Immunohistochemical analysis of elastin was performed using liver tissue sections of IPH patients. IPH sera contained one or more AECA that could bind to the vascular endothelial cells of the peripheral portal tracts of the liver. When the value of AECA greater than the mean + 2SD of healthy control was regarded as positive, the positive detection rate of either IgG, IgA or IgM AECA in IPH sera was 30% (10 of 33 case... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5431044 Mon, 21 Nov 2011 23:50:27 +0100 5431044 http://www.medworm.com/index.php?rid=5431047&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04527.x Conclusions: HAE patients have enhanced production of autoantibodies most probably due to the increased activation of B cells which was found to be in association with a high expression of TLR‐9. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5431047 Mon, 21 Nov 2011 05:00:00 +0100 5431047 http://www.medworm.com/index.php?rid=5431046&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04528.x SUMMARYThe immune receptor expressed on myeloid cells 1 (IREM‐1/CD300F) has been shown to inhibit various inflammatory processes in myeloid cells such as macrophages and mast cells. IREM‐1 exerts its inhibitory effect through its intracellular immunoreceptor tyrosine‐based inhibition motifs (ITIMs). In order to generate immunomodulatory molecules that can regulate the inflammatory activation of macrophages, decapeptides representing each of the 5 ITIM‐like sequences in the cytoplasmic tail of IREM‐1 were synthesized in conjugation with HIV‐TAT48‐57, which was added to promote internalization of the peptides. Interestingly, all of these TAT‐ITIM fusion peptides inhibited Toll‐like receptor (TLR)‐mediated production of pro‐inflammatory molecules including matrix metallo... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5431046 Mon, 21 Nov 2011 05:00:00 +0100 5431046 http://www.medworm.com/index.php?rid=5431045&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04529.x Conclusions: We consider the bronchial and alveolar fraction to be lavage fluid from fundamentally different compartments and recommend analysis of the alveolar fraction in diagnostic work‐up of ILD. In addition, our data suggest that age corrected BAL fluid CD4+/CD8+ ratios should be used in the clinical evaluation of patients with interstitial lung diseases. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5431045 Mon, 21 Nov 2011 05:00:00 +0100 5431045 http://www.medworm.com/index.php?rid=5421233&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04526.x Conclusions: Innate immunity defects appear to be present in HIV positive patients, regarding phagocytic activity and oxidative burst of monocytes and neutrophils. These defects are greatly influenced by the level of treatment efficacy, with emphasis on CD4 cell counts and viral load. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5421233 Fri, 18 Nov 2011 23:50:01 +0100 5421233 http://www.medworm.com/index.php?rid=5421235&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04525.x AbstractComplete complement component 6 deficiency (C6Q0) is a co‐dominant genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. Affected individuals have two affected alleles and can be homozygous or compound heterozygous for the particular gene defects they carry. This disorder has been diagnosed relatively frequently in Western Cape, South Africans.Affected patients are prescribed penicillin prophylaxis. In 2004 we commenced a clinical follow‐up study of 46 patients.Of these, 43 had family age‐matched C6 sufficient controls. Participants were classified as either (i) Well, or (ii) having a Serious Illness or Died (SI/D). A SI was a long‐term illness that did not allow the performance of normal daily activities. Among 43 patients, 2... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5421235 Thu, 17 Nov 2011 05:00:00 +0100 5421235 http://www.medworm.com/index.php?rid=5406475&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04524.x Conclusions: Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5406475 Wed, 16 Nov 2011 05:39:09 +0100 5406475 http://www.medworm.com/index.php?rid=5399823&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04480.x SummaryDendritic cells (DCs) are professional antigen‐presenting cells capable of initiating primary/adaptive immune responses and tolerance. DC functions are regulated by their state of maturation. However, the molecular pathways leading to DC development and maturation remain poorly understood. We attempted to determine whether inhibition of nuclear factor kappa B (NF‐κB), which is one of the pivotal pathways underlying these processes, could induce immunophenotypic and functional changes in lipopolysaccharide‐induced mature DCs derived from murine bone marrow. A comparative in vitro study of five clinically used drugs that are known to inhibit NF‐κB demonstrated that azithromycin, a macrolide antibiotic, significantly inhibited expression of co‐stimulatory molecules (CD40 an... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399823 Sat, 12 Nov 2011 23:51:50 +0100 5399823 http://www.medworm.com/index.php?rid=5399822&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04467.x SummaryThe 19‐kDa C‐terminal region of merozoite surface protein 1 (MSP119), a major blood stage malaria vaccine candidate, is the target of cellular and humoral immune responses in humans naturally infected with Plasmodium falciparum. We have previously described engineered variants of this protein, designed to be better vaccine candidates, but the human immune response to these proteins has not been characterized fully. Here we have investigated the antigenicity of one such variant compared to wild‐type MSP119‐derived protein and peptides. Gambian adults produced both high T helper type 1 (Th1) [interferon (IFN)‐γ] and Th0/Th2 [interleukin (IL)‐13 and sCD30] responses to the wild‐type MSP119 and the modified protein as wells as to peptides derived from both forms. Response... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399822 Sat, 12 Nov 2011 23:51:45 +0100 5399822 http://www.medworm.com/index.php?rid=5399821&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04477.x SummaryAntibody‐dependent cell‐mediated cytotoxicity (ADCC), which links the innate and the adaptive arms of immunity, is a major host immunosurveillance mechanism against tumours, as well as the leading mechanism underlying the clinical efficacy of therapeutic antibodies such as cetuximab and trastuzumab, which target tumour antigens, human epidermal growth factor receptor (HER)1 and HER2, respectively. Immunoglobulin (Ig)G antibody‐mediated ADCC is triggered upon ligation of Fcγ receptor (FcγR) to the Fc region of IgG molecules. It follows that genetic variation in FcγR and Fc could contribute to the differences in the magnitude of ADCC. Genetic variation in FcγR is known to contribute to the differences in the magnitude of ADCC, but the contribution of natural genetic variatio... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399821 Sat, 12 Nov 2011 23:51:44 +0100 5399821 http://www.medworm.com/index.php?rid=5399820&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04476.x SummaryIntravenous immunoglobulin (IVIg) is used for the treatment of an increasing number of autoimmune diseases. Clinical observations on IVIg‐treated patients have revealed a modulation of T cell populations and functions in these patients. In vitro studies aimed at understanding the mechanisms underlying the effects of IVIg on T cells led to the conclusion that IVIg directly affected lectin‐activated T cell functions. However, more recent studies have suggested the absence of a direct effect of IVIg on T cells. In the present work, we revisited the effect of IVIg on T cells using lectin‐stimulated human T cells and showed that IVIg inhibited T cell functions only when added simultaneously with the activating lectin. Further, we showed that IVIg depleted from lectin‐reactive IgG... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399820 Sat, 12 Nov 2011 23:51:42 +0100 5399820 http://www.medworm.com/index.php?rid=5399819&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04468.x SummaryIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown aetiology. Interleukin (IL)‐1β plays an important role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL‐1β and IL‐1 receptor antagonist (IL‐1Ra) in bronchoalveolar lavage fluid (BALF) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels. In 77 IPF patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B genes were determined. Serum and BALF IL‐1Ra and IL‐1β levels were measured using a multiplex suspension bead array system and were correlated with genotypes. Both in serum and BALF a significantly dec... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399819 Sat, 12 Nov 2011 23:51:40 +0100 5399819 http://www.medworm.com/index.php?rid=5399818&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04484.x SummaryIt has long been known that tumour necrosis factor (TNF)/TNFRSF1A signalling is involved in the pathophysiology of multiple sclerosis (MS). Different genetic and clinical findings over the last few years have generated renewed interest in this relationship. This paper provides an update on these recent findings. Genome‐wide association studies have identified the R92Q mutation in the TNFRSF1A gene as a genetic risk factor for MS (odds ratio 1·6). This allele, which is also common in the general population and in other inflammatory conditions, therefore only implies a modest risk for MS and provides yet another piece of the puzzle that defines the multiple genetic risk factors for this disease. TNFRSF1A mutations have been associated with an autoinflammatory disease known as TNF r... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399818 Sat, 12 Nov 2011 23:51:38 +0100 5399818 http://www.medworm.com/index.php?rid=5399817&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04482.x In conclusion, the major risk alleles of AMD in CFH do not have a similar effect on developing RA. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399817 Sat, 12 Nov 2011 23:51:35 +0100 5399817 http://www.medworm.com/index.php?rid=5399816&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04481.x SummaryType 1 diabetes (T1D) is an autoimmune disease that destroys the insulin‐producing beta‐islet cells of the pancreas. Currently, there are no treatment modalities for prevention of T1D, and the mechanisms influencing disease inception and early progression are not well understood. We have used the insulin 2−/− non‐obese diabetic (Ins2−/− NOD) model to study stages of T1D and to examine the protective effects of a potent analogue of 1α,25‐dihydroxyvitamin D3, 2α‐methyl‐19‐nor‐(20S)‐1α,25‐dihydroxyvitamin D3 (2AMD). Pancreatic tissues from control and 2AMD‐treated Ins2−/− NOD mice were obtained weekly from 5 to 16 weeks of age. Using immunohistochemical (IHC) analysis, samples were analysed for changes in beta cell survival, islet structure and T ce... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399816 Sat, 12 Nov 2011 23:51:34 +0100 5399816 http://www.medworm.com/index.php?rid=5399815&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04479.x SummaryHighly sensitive and specific radioimmunoassays have been validated for autoantibodies reacting with the four major autoantigens identified so far in autoimmune diabetes. However, the analysis of this large number of autoantigens has increased the costs and time necessary for complete autoantibody screenings. Our aim was to demonstrate that it is possible to detect the immunoreactivity against a combination of four different autoantigens by a single assay, this representing a rapid, low‐cost first approach to evaluate humoral autoimmunity in diabetes. By using this novel multi‐autoantigen radioimmunoassay (MAA), in subsequent steps we analysed 830 sera, 476 of known and 354 of unknown diabetes‐specific immunoreactivity, collected from various groups of individuals including ty... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399815 Sat, 12 Nov 2011 23:51:32 +0100 5399815 http://www.medworm.com/index.php?rid=5399814&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04478.x SummarySjögren's syndrome (SS) is a chronic autoimmune disease characterized by a progressive oral and ocular dryness that correlates poorly with the autoimmune damage of the glands. It has been proposed that a loss of homeostatic equilibrium in the glands is partly responsible for salivary dysfunction with acinar cells involved actively in the pathogenesis of SS. The non‐obese diabetic (NOD) mouse model of Sjögren's syndrome develops secretory dysfunction and early loss of glandular homeostatic mechanisms, with mild infiltration of the glands. Based on the vasodilator, prosecretory and trophic effects of the vasoactive intestinal peptide (VIP) on acini as well as its anti‐inflammatory properties we hypothesized that the local expression of VIP/vasoactive intestinal peptide receptor ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399814 Sat, 12 Nov 2011 23:51:30 +0100 5399814 http://www.medworm.com/index.php?rid=5399804&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04523.x SummaryEnterocytes used to be studied especially in terms of digestion protagonists. But, as the immune functions of the intestinal tract were better understood, it became clear that enterocytes are not mere bystanders in what concerns the induction of immune tolerance to dietary peptides and gut microbiota. In fact, enterocytes are actively involved in shaping the intestinal immune environment, designed for maintaining a non‐belligerent state. This tolerant milieu of the gut immune system is achieved by keeping a balance between suppression and stimulation of the inflammatory responses. Our review presents the current state of knowledge concerning the relationship between enterocytes and immune cells (dendritic cells, lymphocytes), with emphasis on the enterocytes′ impact on the mecha... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399804 Sat, 12 Nov 2011 23:50:21 +0100 5399804 http://www.medworm.com/index.php?rid=5399808&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04519.x Conclusions: Our results show that glycine, histidine, and cysteine can inhibit NF‐κB activation, IκBα degradation, CD62E expression, and IL‐6 production in HCAECs, suggesting that these amino acids may exhibit anti‐inflammatory effects during endothelial inflammation. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399808 Thu, 10 Nov 2011 05:00:00 +0100 5399808 http://www.medworm.com/index.php?rid=5399807&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04520.x In this study, we investigated the role and expression of Th17 cells and Th17 cytokines in human tuberculosis. We show that the basal proportion of IFN‐γ‐, IL‐17‐ and IL‐22‐expressing CD4+ T cells and IL‐22 expressing granulocytes in peripheral blood were significantly lower in latently infected healthy individuals and active tuberculosis patients compared to healthy controls. In contrast, CD4+ T cells expressing IL‐17, IL‐22 and IFN‐γ were significantly increased following mycobacterial antigens stimulation in both latent and actively infected patients. Interestingly, proinflammatory IFN‐γ and TNF‐α were increased following antigen stimulation in latent infection. Similarly, IL‐1β, IL‐4, IL‐8, IL‐22 and TNF‐α were increased in the serum of latently ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399807 Thu, 10 Nov 2011 05:00:00 +0100 5399807 http://www.medworm.com/index.php?rid=5399806&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04522.x AbstractBy definition allergens are proteins with the ability to elicit powerful T helper lymphocyte Type 2 (Th2) responses, culminating in IgE antibody production. Why specific proteins cause aberrant immune responses has remained largely unanswered. Recent data suggest that there may be several molecular paths that may affect allergenicity of proteins. The focus of this study is the response of airway epithelium to a major allergen from Phleum pratense Phl p 1. Instead of focussing on a few genes and proteins that might be affected by the major allergen our aim was to obtain a broader view on the immune stimulatory capacity of Phl p 1. We therefore performed detailed analysis on mRNA and protein level by using a microarray approach to define Phl p 1‐induced gene expression. We found th... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399806 Thu, 10 Nov 2011 05:00:00 +0100 5399806 http://www.medworm.com/index.php?rid=5399805&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04521.x SummarySurfactant protein D (SP‐D), a member of the C‐type lectin (collectin) protein family, plays a critical role in innate host defense against various microbial pathogens and in the modulation of inflammatory responses in the lung. However, little is known about its expression and biological function in the kidney. In this work, we studied SP‐D expression in human kidney and cultured human renal proximal tubular epithelial cells (HK‐2), and examined the effect of SP‐D on proinflammatory cytokine production after lipopolysaccharide (LPS) stimulus. We observed the expression of both SP‐D mRNA and protein in human kidney and in vitro HK‐2 cells by immunohistochemistry, Western blot analysis, reverse transcription PCR, and real‐time PCR. To explore the potential role of SP�... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399805 Thu, 10 Nov 2011 05:00:00 +0100 5399805 http://www.medworm.com/index.php?rid=5399813&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04514.x SummaryDespite complex genomic and epigenetic abnormalities, many cancers are irrevocably dependent on an initiating oncogenic lesion whose restoration to a normal physiologic activation can elicit a dramatic and sudden reversal of their neoplastic properties. This phenomenon of the reversal of tumorigenesis has been described as oncogene addiction [1]. Oncogene addiction had been thought to occur largely through tumor cell‐autonomous mechanisms such as proliferative arrest, apoptosis, differentiation and cellular senescence [2‐5]. However, the immune system plays an integral role in almost every aspect of tumorigenesis including tumor initiation [6‐7], prevention [8] and progression [9] as well as the response to therapeutics [10‐12]. Here we highlight more recent evidence suggest... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399813 Mon, 31 Oct 2011 04:00:00 +0100 5399813 http://www.medworm.com/index.php?rid=5399812&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04515.x AbstractMononuclear phagocytes are cells of the innate immunity that defend the host against harmful pathogens and heal tissues after injury. Contrary to expectations, in malignancies, Tumour‐Associated Macrophages (TAM) promote disease progression by supporting cancer cell survival, proliferation and invasion. TAM and related myeloid cells (Tie2+ monocytes and MDSC) also promote tumour angiogenesis and suppress adaptive immune responses. These divergent biological activities are mediated by macrophages/myeloid cells with distinct functional polarization, which are ultimately dictated by micro‐environmental cues. Clinical and experimental evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targetin... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399812 Mon, 31 Oct 2011 04:00:00 +0100 5399812 http://www.medworm.com/index.php?rid=5399811&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04516.x AbstractResearch into aberrant glycosylation and over‐expression of glycolipids on the surface of the majority of cancers, coupled with a knowledge of glycolipids as functional molecules involved in a number of cellular physiological pathways has provided a novel area of targets for cancer immunotherapy. This has resulted in the development of a number of vaccines and monoclonal antibodies that are showing promising results in recent clinical trials. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399811 Mon, 31 Oct 2011 04:00:00 +0100 5399811 http://www.medworm.com/index.php?rid=5399810&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04517.x (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399810 Mon, 31 Oct 2011 04:00:00 +0100 5399810 http://www.medworm.com/index.php?rid=5399809&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04518.x This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to fluorometrically record their effect on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in‐situ from sodium hypochlorite), established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which due to the lack of a functional NADPH oxidase... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5399809 Mon, 31 Oct 2011 04:00:00 +0100 5399809 http://www.medworm.com/index.php?rid=5358553&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04513.x Conclusions: High CMV antibody titers are independently associated with blood pressure and brachial artery flow‐mediated dilation in young men. This association supports the hypothesis that common CMV infection and/or an immune response to CMV may lead to impaired vascular function at a young age. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5358553 Sun, 30 Oct 2011 22:49:29 +0100 5358553 http://www.medworm.com/index.php?rid=5358558&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04508.x AbstractThe immunologic hallmark of Omenn syndrome (OS) is the expansion and activation of an oligoclonal population of auto‐reactive T cells. These cells should rapidly be controlled by immunosuppressive agents, such as cyclosporine A (CsA), to avoid tissue infiltration and to improve the general outcome of the patients. Here we studied the clinical and the immune response to CsA in two Omenn patients and also examined the gene expression profile associated with good clinical response to such therapy. T cell receptor diversity was studied in cells obtained from OS patients during CsA therapy. Characterization of gene expression in these cells was carried out by using the TaqMan Low‐Density Array. One patient showed complete resolution of his symptoms after CsA therapy. The other patie... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5358558 Fri, 28 Oct 2011 04:00:00 +0100 5358558 http://www.medworm.com/index.php?rid=5358557&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04509.x Conclusion: Galectin‐3 is constitutively expressed in cord blood of neonates and seems to play a role in innate immunity of this population. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5358557 Fri, 28 Oct 2011 04:00:00 +0100 5358557 http://www.medworm.com/index.php?rid=5358556&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04510.x AbstractUp‐regulation of interleukin (IL)‐17 in small intestinal mucosa has been reported in celiac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL‐17 immunity in different stages of CD including transglutaminase antibody (TGA) positive children with potential CD, children with untreated and gluten‐free diet treated CD, and in children with T1D. Immunohistochemistry was used for identification of IL‐17 and forkhead box P3 (FOXP3) positive cells and qPCR for IL‐17, FOXP3, retinoic acid related orphan receptor (ROR)c and interferon (IFN)‐γ transcripts. IL‐1beta, IL‐6 and IL‐17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl‐2, was evaluated in IL‐17 stimulated CaCo‐2 cells. The... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5358556 Fri, 28 Oct 2011 04:00:00 +0100 5358556 http://www.medworm.com/index.php?rid=5358555&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04511.x AbstractInsulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and nonalcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. NKT cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin‐deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0.1 mg bovine colostrum prepared from non‐immunized cows, 0.1 mg hyperimmune colostrum raised against a bacterial LPS extract or 0.001, 0.1 or 1 mg ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5358555 Fri, 28 Oct 2011 04:00:00 +0100 5358555 http://www.medworm.com/index.php?rid=5358554&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04512.x SummaryThe pattern recognition molecules H‐ficolin, L‐ficolin and M‐ficolin bind to micro‐organisms. They activate the lectin pathway of complement through MBL‐associated serine proteases (MASPs). Association between low MBL levels and infections in patients undergoing chemotherapy for haematological diseases was previously observed. We now examine for MASP‐2, MASP‐3 and ficolin levels.We assessed the concentration of lectin pathway molecules as risk factors for infection in patients with haematological malignancy undergoing chemotherapy. Samples taken before the initiation of chemotherapy covering 117 chemotherapy cycles in 105 patients were available. MASPs and ficolins were measured by time‐resolved immunoflourometric assays and the levels related to parameters of infect... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5358554 Fri, 28 Oct 2011 04:00:00 +0100 5358554 http://www.medworm.com/index.php?rid=5334763&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04507.x SummaryAbnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multicolour flow cytometry (MFC) in a cohort of well characterised CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) as compared to normal controls (P < 0.0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P= 0.0034). The previously published associations wi... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5334763 Fri, 21 Oct 2011 22:50:37 +0100 5334763 http://www.medworm.com/index.php?rid=5334764&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04506.x SummaryTCR transgenic (TCR‐Tg) mice specific for the arthritogenic 5/4E8 epitope in the G1 domain of cartilage proteoglycan were generated and backcrossed into arthritis‐prone BALB/c background. Although over 90% of CD4+ T cells of all TCR‐Tg lines were 5/4E8‐specific, one (TCR‐TgA) was highly sensitive to G1‐induced‐ or spontaneous arthritis, while another (TCR‐TgB) was less susceptible. Here we studied if fine differences in TCR signaling controlled the onset and severity of arthritis.Mice from the two TCR‐Tg lines were immunized side‐by‐side with purified recombinant human G1 (rhG1) domain for GIA. TCR‐TgA mice developed severe and early‐onset arthritis, whereas TCR‐TgB mice developed weaker arthritis with delayed onset, although TCR‐TgB CD4+ T cells expres... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5334764 Tue, 18 Oct 2011 04:00:00 +0100 5334764 http://www.medworm.com/index.php?rid=5313608&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04505.x SummaryIn systemic lupus erythematosus (SLE), the auto antibodies that form immune complexes (ICs) trigger activation of the complement system. This results in the formation of membrane attack complex (MAC) on cell membrane and the soluble terminal complement complex (TCC). Hyperactive T cell responses are hallmark of SLE pathogenesis. How complement activation influences the T cell responses in SLE is not fully understood. We observed that aggregated human γ‐globulin (AHG) bound to a subset of CD4+T cells in peripheral blood mononuclear cells and this population increased in the SLE patients. Human naïve CD4+ T cell, when treated with purified ICs and TCC triggered recruitment of the FcR γ chain with the membrane receptor and co‐localized with phosphorylated Syk. These events were ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5313608 Fri, 14 Oct 2011 22:50:45 +0100 5313608 http://www.medworm.com/index.php?rid=5313614&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04499.x AbstractThere is no approved therapy for food allergy. The current standard of care is elimination of the triggering food from the diet and accessibility to epinephrine. Immunotherapy is a promising treatment approach. While desensitization to most foods seems feasible, it remains unclear if a permanent state of tolerance is achievable. The research team at Duke is pioneering immunotherapy for food allergies. Work here has evolved over time from small open‐label pilot studies to larger randomized designs. Our data shows that immunologic changes associated with immunotherapy include reduction in mast cell reactivity, decreased basophil responses, decreased specific‐IgE, increased IgG4, and induction of regulatory T cells. Immunotherapy has generated much excitement in the food allergy c... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5313614 Wed, 12 Oct 2011 04:00:00 +0100 5313614 http://www.medworm.com/index.php?rid=5313613&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04500.x AbstractInvariant natural killer T (iNKT) cells have been shown to play a key role in the regulation of immunity in health and disease. However, iNKT cell responses have also been found to influence both rejection and the induction of tolerance following transplantation of allogeneic cells or organs. Although a number of mechanisms have been identified that lead to iNKT cell activation, how iNKT cells are activated following transplantation remains unknown. This review will attempt to identify potential mechanisms of iNKT cell activation in the context of transplantation by applying knowledge garnered from other disease situations. Furthermore, we put forward a novel mechanism of iNKT cell activation which we believe may be the dominant mechanism responsible for iNKT activation in this set... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5313613 Wed, 12 Oct 2011 04:00:00 +0100 5313613 http://www.medworm.com/index.php?rid=5313612&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04501.x (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5313612 Wed, 12 Oct 2011 04:00:00 +0100 5313612 http://www.medworm.com/index.php?rid=5313611&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04502.x AbstractHerpes virus infections are chronic and coexist with acquired immune responses that generally prevent severe damage to the host, while allowing periodic shedding of virus and maintenance of its transmission in the community. Herpes simplex viruses type 1 and 2 (HSV‐1, HSV‐2) are typical in this regard and are representative of the viral subfamily Alphaherpesvirinae, which has a tropism for neuronal and epithelial cells. This review will emphasize recent progress in decoding the physiologically important CD8+ and CD4+ T‐cell responses to HSV in humans. The expanding data set is discussed in the context of the search for an effective HSV vaccine to as therapy for existing infections and to prevent new infections. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5313611 Wed, 12 Oct 2011 04:00:00 +0100 5313611 http://www.medworm.com/index.php?rid=5313610&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04503.x AbstractAllergen specific immunotherapy has been effectively utilized as a clinical treatment for hypersensitivity to many allergens. Studies on suppression of basophil activation during immunotherapy have provided insight into underlying immune mechanisms and support the potential use of basophil activation as a biomarker of clinical outcomes. This review examines the evidence for different pathways of basophil modulation associated with various forms of immunotherapy. Better understanding of the molecular mechanisms of basophil activation and desensitization and the relationship between suppression of these effector cells to clinical outcomes hold promise for further development and improvement in potential therapies for allergic diseases. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5313610 Wed, 12 Oct 2011 04:00:00 +0100 5313610 http://www.medworm.com/index.php?rid=5313609&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04504.x This study was conducted to document the proportion of CD4+/IL‐17A+–, CD16+/IDO+–, Foxp3+–expressing cells, senescent cells (p16INK4α), and the percentage of interstitial fibrosis (IF) in graft biopsies of kidney transplant recipients participating in the BENEFIT (Bristol‐Myers Squibb IM103008) study. CD4+/IL‐17A+, CD16+/IDO+, Foxp3+, and p16INK4α+cells were evaluated by immunohistochemistry, and the percentage of IF by morphometry on graft biopsies obtained at time 0 (pre‐implantation) and at 12 months post‐transplant. Senescent cells and CD4+/IL‐17A+ cells were increased among graft biopsies in subjects receiving cyclosporine A (CsA) compared to those under Belatacept treatment. Meanwhile, CD16+/IDO+ and Foxp3+–expressing cells were lower in biopsies from CsA treatm... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5313609 Wed, 12 Oct 2011 04:00:00 +0100 5313609 http://www.medworm.com/index.php?rid=5303824&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04475.x SummaryDehydroxymethylepoxyquinomicin (DHMEQ), a new nuclear factor (NF)‐κB inhibitor, has several beneficial effects, including the suppression of tumour growth and anti‐inflammatory effects. DHMEQ can also suppress the production of tumour necrosis factor (TNF)‐α induced by lipopolysaccharide (LPS) in vitro. In the present study, we examine the effects of DHMEQ on TNF‐α production in vivo and on the survival of mice injected with LPS. When DHMEQ was injected into mice 2 h before LPS injection, the survival of the LPS‐injected mice was prolonged. When DHMEQ was injected twice (2 h before LPS injection and the day after LPS injection), all the mice were rescued. The injection of DHMEQ 1 h after LPS injection and the day after LPS injection also resulted in the rescue of ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303824 Tue, 11 Oct 2011 22:52:56 +0100 5303824 http://www.medworm.com/index.php?rid=5303823&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04471.x SummaryMechanisms associated with the progression of simple steatosis to non‐alcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (Tregs) play a critical role in regulating inflammatory processes in non‐alcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose Treg‐mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (HF) diet for 8 weeks. Mice in the HF group had a significantly higher frequency of liver Th17 cells compared to ND‐fed mice. Neutralization of interleukin (IL)‐17 in HF mice ameliorated lipopolysaccharide (LPS)‐induced liver injury reflected by decreased serum alanine aminotransferase (ALT) levels an... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303823 Tue, 11 Oct 2011 22:52:52 +0100 5303823 http://www.medworm.com/index.php?rid=5303822&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04462.x SummaryGraft‐versus‐host disease (GVHD) is a life‐threatening complication of human allogeneic haematopoietic stem cell transplantation. Non‐obese diabetic (NOD)‐scid IL2rγnull (NSG) mice injected with human peripheral blood mononuclear cells (PBMC) engraft at high levels and develop a robust xenogeneic (xeno)‐GVHD, which reproduces many aspects of the clinical disease. Here we show that enriched and purified human CD4 T cells engraft readily in NSG mice and mediate xeno‐GVHD, although with slower kinetics compared to injection of whole PBMC. Moreover, purified human CD4 T cells engraft but do not induce a GVHD in NSG mice that lack murine MHC class II (NSG‐H2‐Ab1 tm1Gru, NSG‐Ab°), demonstrating the importance of murine major histocompatibility complex (MHC) class II ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303822 Tue, 11 Oct 2011 22:52:51 +0100 5303822 http://www.medworm.com/index.php?rid=5303821&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04458.x SummaryConcanavalin A (Con A)‐induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c+ I‐Alow B220+); however, conventional DC were CD11c+ I‐Ahigh B220–. At an early stage (3–6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12–24 h) in parallel with hepatic failure. The hepatic CD11c+ DC population contained many CD11b‐ cells, while the majority of splenic CD11c+ DC were CD11b+. After Con A administration, the proportion of I‐A+ and CD11b+ cells within the CD11c+ DC population tended to increase in the liver, but not in the s... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303821 Tue, 11 Oct 2011 22:52:49 +0100 5303821 http://www.medworm.com/index.php?rid=5303820&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04457.x SummaryToll‐like receptors are pattern‐recognition receptors of the innate immune system that are activated during viral, bacterial or other infections, as well as during disease progression of type 1 and type 2 diabetes. Toll‐like receptor 5 (TLR‐5) specifically recognizes bacterial infection through binding of flagellin from pathogenic bacteria such as Salmonella and Listeria species. We have found that the expression of TLR5 is up‐regulated by glucose activation of isolated islets of Langerhans, in contrast to other investigated TLRs (TLR‐2, ‐3, ‐4, ‐6 and ‐9. Stimulation of islets with 10 mm glucose increased the levels of TLR5 mRNA 10‐fold (P = 0·03) and the TLR‐5 protein levels twofold (P = 0·04). Furthermore, the protein level of downstream signal... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303820 Tue, 11 Oct 2011 22:52:47 +0100 5303820 http://www.medworm.com/index.php?rid=5303819&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04452.x SummaryMyeloid FcαRI, a receptor for immunoglobulin (Ig)A, mediates cell activation or inhibition depending on the type of ligand interaction, which can be either multivalent or monovalent. Anti‐inflammatory signalling is triggered by monomeric targeting using anti‐FcαRI Fab or IgA ligand binding, which inhibits immune and non‐immune‐mediated renal inflammation. The participation of Toll‐like receptors (TLRs) in kidney pathology in experimental models and various forms of human glomerular nephritis has been discussed. However, little is known about negative regulation of innate‐immune activation. In the present study, we generated new transgenic mice that express FcαRIR209L/FcRγ chimeric protein and showed that the monovalent targeting of FcαRI exhibited inhibitory effects... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303819 Tue, 11 Oct 2011 22:52:46 +0100 5303819 http://www.medworm.com/index.php?rid=5303818&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04437.x SummaryExperimental crescentic glomerulonephritis is driven by systemic cellular immune responses. A pathogenic role for T helper type 1 (Th1) and Th17 cells is well established. T‐bet, a key transcription factor required for Th1 lineage commitment, and retinoic acid‐related orphan receptor‐γt (Rorγt), a key Th17 transcription factor, are required for full expression of disease. Similarly, several Th1‐ and Th17‐associated cytokines have been implicated in disease augmentation. The role of Th2 cells in the disease is less clear, although Th2‐associated cytokines, interleukin (IL)‐4 and IL‐10, are protective. We sought to determine the role of signal transducer and activation of transcription 6 (STAT6), a key regulator of Th2 responses, in experimental crescentic glomerulon... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303818 Tue, 11 Oct 2011 22:52:44 +0100 5303818 http://www.medworm.com/index.php?rid=5303817&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04474.x SummaryCytokine and chemokine levels were studied in infants (<5 years) with uncomplicated (MM) and severe malaria tropica (SM), and in Plasmodium falciparum infection‐free controls (NEG). Cytokine plasma levels of interleukin (IL)‐10, IL‐13, IL‐31 and IL‐33 were strongly elevated in MM and SM compared to NEG (P < 0·0001). Inversely, plasma concentrations of IL‐27 were highest in NEG infants, lower in MM cases and lowest in those with SM (P < 0·0001, NEG compared to MM and SM). The levels of the chemokines macrophage inflammatory protein (MIP3)‐α/C–C ligand 20 (CCL20), monokine induced by gamma interferon (MIG)/CXCL9 and CXCL16 were enhanced in those with MM and SM (P < 0·0001 compared to NEG), and MIP3‐α/CCL20 and MIG/CXCL9 were correlated po... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303817 Tue, 11 Oct 2011 22:52:42 +0100 5303817 http://www.medworm.com/index.php?rid=5303816&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04463.x The objective of this study was to distinguish immune signatures in HIV controllers and progressors, by evaluating tolerogenic and immunogenic factors in untreated HIV‐1 infected individuals. The recruited population was divided into putative elite controllers (PEC), long‐term non‐progressors (LTNP), normal progressors (NP) and fast progressors (FP). The proportion of regulatory T cells [Tregs, CD4+CD25+forkhead box P3 (FoxP3+)], programmed death (PD)‐1 and cytotoxic T lymphocyte antigen (CTLA)‐inhibitory molecules and CD40L, CD69 and Ki67 activation markers were evaluated in peripheral blood mononuclear cells (PBMC) by flow cytometry. Significant differences were found between HIV controllers and HIV progressors, with up‐regulation of Tregs, PD‐1 and CTLA‐4 and decrease of... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303816 Tue, 11 Oct 2011 22:52:40 +0100 5303816 http://www.medworm.com/index.php?rid=5303815&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04451.x In this study we investigate the phenotype of Tregs in the context of human immunodeficiency virus (HIV)‐1 infection, and the function of these cells in response to HIV‐1‐Gag and cytomegalovirus (CMV) peptides. Phenotypic data demonstrate a decrease in forkhead box transcription factor 3 (FoxP3+) Treg numbers in the peripheral blood of HIV‐1+ individuals compared to healthy controls, which is most pronounced in those with high HIV‐1 RNA plasma load. Due to aberrant expression of CD27 and CD127 during HIV‐1 disease, these markers are unreliable for Treg identification. The CD3+CD4+CD25hiCD45RO+ phenotype correlated well with FoxP3 expression in both the HIV‐1+ and seronegative control cohorts. We observed expression of CD39 but not CD73 on Tregs from HIV‐1+ and healthy contr... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303815 Tue, 11 Oct 2011 22:52:37 +0100 5303815 http://www.medworm.com/index.php?rid=5303814&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04409.x SummaryCompounds targeting the chemokine receptor CCR5 have recently been approved for treatment of human immunodeficiency virus (HIV) infection. Given the central role of CCR5 in inflammation and recruitment of antigen‐presenting cells (APC), it is important to investigate the immunological consequences of pharmacological inhibition of CCR5. We evaluated the in vitro effect of different concentrations of CCR5 antagonist maraviroc (MVC) on cell migration of monocytes, macrophages (MO) and monocyte‐derived dendritic cells (MDC) towards peptide formyl‐methionyl‐leucyl‐phenylalanine (fMLP) and chemokines regulated upon activation normal T cell expressed and secreted (RANTES) and CCL4/macrophage inflammatory protein‐1 (MIP‐1β) and CCL2/monocyte chemotactic protein‐1 (MCP‐1).... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303814 Tue, 11 Oct 2011 22:52:35 +0100 5303814 http://www.medworm.com/index.php?rid=5303813&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04465.x SummaryThe signal transducer and activator of transcription 3 (STAT3) transcription factor pathway plays an important role in many biological phenomena. STAT3 transcription is triggered by cytokine‐associated signals. Here, we use isolated human B cells to analyse the role of STAT3 in interleukin (IL)‐10 induced terminal B cell differentiation and in immunoglobulin (Ig)A production as a characteristic readout of IL‐10 signalling. We identified optimal conditions for inducing in‐vitro IgA production by purified blood naive B cells using IL‐10 and soluble CD40L. We show that soluble CD40L consistently induces the phosphorylation of nuclear factor (NF)‐κB p65 but not of STAT3, while IL‐10 induces the phosphorylation of STAT3 but not of NF‐κB p65. Interestingly, while soluble... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303813 Tue, 11 Oct 2011 22:52:33 +0100 5303813 http://www.medworm.com/index.php?rid=5303812&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04472.x SummaryThymoma‐associated multi‐organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft‐versus‐host (GVH)‐like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin‐infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma‐associated multi‐organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma‐associated multi‐organ autoimm... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303812 Tue, 11 Oct 2011 22:52:32 +0100 5303812 http://www.medworm.com/index.php?rid=5303811&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04466.x SummaryAdvanced chronic lymphocytic leukaemia (CLL) is associated with profound immunodeficiency, including changes in T regulatory cells (Tregs). We determined the pattern of expression of forkhead box P3 (FoxP3), CD25, CD27 and CD127 and showed that the frequency of CD4+FoxP3+ T cells was increased in CLL patients (12% versus 8% in controls). This increase was seen only in advanced disease, with selective expansion of FoxP3‐expressing cells in the CD4+CD25low population, whereas the number of CD4+CD25highFoxP3+ cells was unchanged. CD4+CD25low cells showed reduced expression of CD127 and increased CD27, and this regulatory phenotype was also seen on all CD4 T cells subsets in CLL patients, irrespective of CD25 or FoxP3 expression. Incubation of CD4+ T cells with primary CLL tumours led... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303811 Tue, 11 Oct 2011 22:52:30 +0100 5303811 http://www.medworm.com/index.php?rid=5303810&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04464.x In conclusion, these data link the up‐regulation of the eosinophil chemotactic factor CCL26 in BP to the lesional accumulation of activated eosinophils in the skin. Thereby they broaden the understanding of BP pathogenesis and might indicate new options for therapeutic intervention. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303810 Tue, 11 Oct 2011 22:52:28 +0100 5303810 http://www.medworm.com/index.php?rid=5303806&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04498.x This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulfate (DSS)‐induced colitis in mice. Immunocompetent BALB/c and immunodeficient SCID mice reared in SPF (specific‐pathogen‐free) conditions were treated intrarectally with C. tyrobutyricum one week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms – bleeding, rectal prolapses and colitis‐induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both stra... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303806 Tue, 11 Oct 2011 22:51:38 +0100 5303806 http://www.medworm.com/index.php?rid=5303809&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04495.x SummaryDevelopment of high risk combinations of multiple islet autoantibodies and type 1 diabetes is associated with high affinity insulin autoantibodies (IAA), but IAA affinity measurements require large serum volumes. We therefore investigated whether a simplified method of IAA affinity measurement using a low concentration of unlabelled insulin (ULI) competitor discriminated between moderate/high and low affinity IAA and identified individuals at highest risk of disease. Samples were assayed by radiobinding microassay using high (4.0 x 10‐5 mol/l) and low (7 x 10‐9 mol/l) ULI concentrations for competitive displacement in three cohorts of IAA positive individuals; (1) 68 patients with newly‐diagnosed type 1 diabetes, (2) 40 healthy schoolchildren and (3) 114 relatives of patients ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303809 Tue, 11 Oct 2011 04:00:00 +0100 5303809 http://www.medworm.com/index.php?rid=5303808&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04496.x AbstractThe immune‐modulatory effects of probiotics were assessed following exposure of normal PBMC, cord blood cells, and the spleen‐derived monocyte/macrophage cell line CRL‐9850 to Lactobacillus acidophilus LAVRI‐A1, Lactobacillus rhamnosus GG, EPS‐producing Streptococcus thermophilus St1275, Bifidobacteriun longum BL536, Bifidobacteriun lactis B94 and Escherichia coli TG1 strains. Cell production of a panel of pro‐ and anti‐inflammatory cytokines following bacterial stimulation was measured, using live, heat‐killed or mock GIT‐exposed bacteria, and results show that i) all bacterial strains investigated induced significant secretion of pro‐ and anti‐inflammatory cytokines from PBMC‐derived monocytes/macrophages, (ii) cytokine levels increased relative to the exp... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303808 Tue, 11 Oct 2011 04:00:00 +0100 5303808 http://www.medworm.com/index.php?rid=5303807&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04497.x In conclusion, the EGF rs4444903 A>G polymorphism appears to be associated with an unfavourable disease course of chronic HBV infection and cirrhosis development. This effect might be modulated, at least in part, by the gender of the patient. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5303807 Tue, 11 Oct 2011 04:00:00 +0100 5303807 http://www.medworm.com/index.php?rid=5296309&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04492.x Conclusion: The herein reported multiplexing evaluation represents a comprehensive approach in the assessment of genetic conditions affecting the immune system such as the IPEX syndrome, paving the way for the development of diagnostic tools to improve the standard clinical and immunological profiling of the disease. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5296309 Fri, 07 Oct 2011 04:00:00 +0100 5296309 http://www.medworm.com/index.php?rid=5296308&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04493.x AbstractDysregulations concerning the composition and function of regulatory T cells (Tregs) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six‐color flow cytometric analysis to demonstrate that the total CD4+CD127low+/‐CD25+FoxP3+‐Treg cell pool contains four distinct Treg subsets: DRhigh+CD45RA–, DRlow+CD45RA–, DR‐CD45RA–Tregs and naïve DR‐CD45RA+‐Tregs. During the normal course of pregnancy, the most prominent changes in the composition of the total Treg cell pool were observed between the 10th and 20th week of gestation, with a clear decrease in the percentage of DRhigh+CD45RA– and DRlow+CD45RA–Tregs and a clear increase in the percentage of naïve DR‐CD45RA+‐Tregs. After that time, the composition of the total Treg cell... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5296308 Fri, 07 Oct 2011 04:00:00 +0100 5296308 http://www.medworm.com/index.php?rid=5296307&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04494.x In conclusion, the decreased Nck1 protein in Jurkat T cells resulted in an impairment of TCR/CD3‐mediated activation involving a defective Erk phosphorylation pathway. (Source: Clinical and Experimental Immunology) Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5296307 Sat, 01 Oct 2011 04:00:00 +0100 5296307 http://www.medworm.com/index.php?rid=5259775&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04491.x AbstractCarbon Monoxide (CO) is produced during the catabolism of free heme, catalyzed by Heme Oxygenase (HO) enzymes and its physiological roles include vasodilation, neurotransmission, inhibition of platelet aggregation, and anti‐proliferative effects on smooth muscle. In vivo preclinical studies have shown that exogenously‐administered quantities of CO may represent an effective treatment for conditions characterized by a dysregulated immune response. The Carbon Monoxide–Releasing Molecules (CO‐RMs) represent a group of compounds capable of carrying and liberating controlled quantities of CO in the cellular systems.This review covers the physiological and anti‐inflammatory properties of the HO/CO pathway in the Central Nervous System. It also discusses the effects of CORMs in ... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5259775 Wed, 28 Sep 2011 22:51:23 +0100 5259775 http://www.medworm.com/index.php?rid=5259779&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04487.x AbstractReperfusion injury remains one of the major problems in transplantation. Repair from ischemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donors with Rapamycin and Tacrolimus to prevent I/R injury. Twelve hours before nephrectomy, donor received immunosuppressive drugs. Animals were divided in four groups. Group 1 Control: no treatment, Group 2: Rapamycin (2 mg/Kg), Group 3 FK506 (0, 3 mg/kg) and Group 4: FK506 (0, 3 mg/kg) plus Rapamycin (2 mg/Kg). Left kidney was removed and after three hours of cold ischemia, the graft was transplanted. Twenty four hours after transplant, kidney was recovered for histological analysis and cytokine expression. Precondition... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5259779 Mon, 26 Sep 2011 04:00:00 +0100 5259779 http://www.medworm.com/index.php?rid=5259778&cid=s_33580_3_f&fid=33580&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2249.2011.04488.x SummaryThe ready access to commercially available multiplex assays and the importance of inflammation in disease pathogenesis has resulted in an abundance of studies aimed at identifying surrogate biomarkers for different clinically important questions. Establishing a link between a biomarker and disease pathogenesis, however, is quite complex and in some instances this complexity is compounded by post‐translational modifications and the use of immuno‐assays that do not always discriminate between the different forms of the same protein. Herein, we provide a detailed description of an assay system that has been established to discriminate the agonist form of CXCL10 from the NH2‐terminal truncated form of the molecule generated by dipeptidylpeptidase IV (DPP4) cleavage. We demonstrate... Clinical and Experimental Immunology journals http://www.medworm.com/rss/comments.php?id=5259778 Mon, 26 Sep 2011 04:00:00 +0100 5259778