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 'European Journal of Immunology' source. Wed, 08 Feb 2012 06:42:51 +0100 http://www.medworm.com/index.php?rid=5666445&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141926 In conclusion, we propose that A2B receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5666445 Mon, 06 Feb 2012 05:00:00 +0100 5666445 http://www.medworm.com/index.php?rid=5666444&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142004 We report that PKD2‐deficient lymphocytes bound normally to integrin ligands in static and shear flow adhesion assays. They also homed normally to lymphoid organs after adoptive transfer into wild‐type mice. DT40 B cells devoid of any PKD isoforms and primary lymphocytes pretreated with a specific PKD inhibitor bound normally to integrin ligands, indicating that multiple PKD isoforms do not redundantly regulate lymphocyte integrins. In addition, PKD2‐deficient lymphocytes, as well as DT40 cells devoid of any PKD isoforms, could activate Rap1 in response to BCR ligation or phorbol ester treatment. Together, these results show that the PKD family does not play a critical role in lymphocyte integrin‐mediated cell adhesion or lymphocyte trafficking in vivo. (Source: European Journal of... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5666444 Mon, 06 Feb 2012 05:00:00 +0100 5666444 http://www.medworm.com/index.php?rid=5666443&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142226 Transitional and naïve mature peripheral B cells respond very differently to BCR cross‐linking. While transitional B cells undergo apoptosis upon BCR engagement, mature B cells survive and proliferate. This differential response correlates with the capacity of mature, but not transitional B cells to transcribe genes that promote cell survival and proliferation, including those encoding c‐Myc and the Bcl‐2 family members Bcl‐xL and A1. We recently demonstrated that transitional B cells fail to assemble transcriptional machinery at the promoter region of these target genes despite equivalent cytoplasmic signaling and nuclear translocation of key transcription factors including NFĸB and NFAT. The transcription factor MEF2C is regulated by both calcineurin and MAPK signaling pathways... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5666443 Wed, 01 Feb 2012 05:00:00 +0100 5666443 http://www.medworm.com/index.php?rid=5627809&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201290006 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5627809 Thu, 26 Jan 2012 11:21:23 +0100 5627809 http://www.medworm.com/index.php?rid=5627808&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142260 Intravenous immunoglobulin G (IVIg) therapy is widely used to treat autoimmune and inflammatory diseases. Recent evidence suggests that in mice splenic resident cells might be important for the anti‐inflammatory activity of IVIgs in a model of serum transfer arthritis. Splenectomized human immunothrombocytopenia (ITP) patients, however, still respond to IVIg therapy. To investigate whether the requirement of the spleen is essential for mouse ITP we used a passive model of induced ITP and demonstrated that IVIg activity was functional in splenectomized animals. Further analysis showed that the IVIg‐mediated amelioration of platelet phagocytosis was fully dependent on terminal sialic acid residues in the IVIg preparation and could be blocked with a SIGNR1 specific antibody. These results... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5627808 Thu, 26 Jan 2012 11:20:17 +0100 5627808 http://www.medworm.com/index.php?rid=5624677&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266713%26dopt%3DAbstract Authors: Abstract COVER IMAGE: The cover is based on a spinal cord histology section taken from a TNFR2(-/-) mouse adoptively transferred with TNFR2(-/-) Treg cells prior to immunization with MOG(35-55) to induce EAE. The section is stained with Luxol Fast blue to detect demyelination; Luxol Fast Red, which detects inflammatory infiltration, is the counterstain. The image is taken from the article by Tsakiri et al. (pp. 403-412) in which it is shown that TNFR2 on non-haematopoietic cells is necessary for Treg-cell suppressive activity and repression of EAE development. The colour of the image has been digitally altered for the cover. CMV: FINE TUNING THE NK-CELL RESPONSE DURING CHRONIC HEPATITIS INFECTION: Two recent studies reported on the expansion of NKG2C(+) NK cells during ch... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624677 Tue, 24 Jan 2012 20:43:14 +0100 5624677 http://www.medworm.com/index.php?rid=5624676&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266714%26dopt%3DAbstract Authors: Cossarizza A, Radbruch A PMID: 22266714 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624676 Tue, 24 Jan 2012 20:43:04 +0100 5624676 http://www.medworm.com/index.php?rid=5624675&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266715%26dopt%3DAbstract Authors: PMID: 22266715 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624675 Tue, 24 Jan 2012 20:42:54 +0100 5624675 http://www.medworm.com/index.php?rid=5624674&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266716%26dopt%3DAbstract Authors: Soumelis V Abstract The field of vaccine adjuvants has been an area of active research and development because of the need to improve the generation of protective immunity to a large number of pathogens, as well as in diseases such as cancer. Adjuvants can also help induce stronger immune responses with fewer injections, and consequently improve both the feasibility and success rate of large-scale population vaccine campaigns in developing countries. A current challenge is to identify vaccine adjuvants of various classes (cytokines, toll-like receptor ligands, etc.) with specific immune-modulating properties in order to tailor the immune response to certain pathological situations. In this issue, Van Roey et al. [Eur. J. Immunol. 2012. 42: 353-363] explore one of these cha... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624674 Tue, 24 Jan 2012 20:42:44 +0100 5624674 http://www.medworm.com/index.php?rid=5624673&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266717%26dopt%3DAbstract Authors: Luscinskas FW Abstract A major focus of researchers studying leukocyte recruitment has been to identify and understand how cell surface endothelial adhesion molecules, cell-to-cell junctional protein complexes, secreted chemokines and chemoattractants, and the vessel basement membrane structure organization coordinate the process of leukocyte recruitment. As research expands beyond the components initially identified as being necessary for leukocyte recruitment, attention has turned to the structures that regulate endothelial cell-to-matrix adhesion. In this issue of the European Journal of Immunology, Parsons et al. [Eur. J. Immunol. 2012. 42: 436-446] identify new players in the regulation of neutrophil diapedesis (transendothelial migration), namely the focal adhesion p... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624673 Tue, 24 Jan 2012 20:42:34 +0100 5624673 http://www.medworm.com/index.php?rid=5624672&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266718%26dopt%3DAbstract Authors: PMID: 22266718 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624672 Tue, 24 Jan 2012 20:42:24 +0100 5624672 http://www.medworm.com/index.php?rid=5624671&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266719%26dopt%3DAbstract Authors: Tsakiri N, Papadopoulos D, Denis MC, Mitsikostas DD, Kollias G Abstract The cover is based on a spinal cord histology section taken from a TNFR2(-/-) mouse adoptively transferred with TNFR2(-/-) Treg cells prior to immunization with MOG(35-55) to induce EAE. The section is stained with Luxol Fast blue to detect demyelination; Luxol Fast Red, which detects inflammatory infiltration, is the counterstain. The image is taken from the article by Tsakiri et al. (pp. 403-412) in which it is shown that TNFR2 on non-haematopoietic cells is necessary for Treg-cell suppressive activity and repression of EAE development. The colour of the image has been digitally altered for the cover. PMID: 22266719 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624671 Tue, 24 Jan 2012 20:42:12 +0100 5624671 http://www.medworm.com/index.php?rid=5619510&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201041303 In this study, we examined several focal adhesion proteins during an inflammatory response. We found that there was selective loss of paxillin and focal adhesion kinase (FAK) from focal adhesions in proximity to transmigrating neutrophils; in contrast the levels of the focal adhesion proteins β1‐integrin and vinculin were unaffected. Paxillin was lost from focal adhesions during neutrophil transmigration both under static and flow conditions. Down‐regulating endothelial paxillin with siRNA blocked neutrophil transmigration while having no effect on rolling or adhesion. As paxillin dynamics are regulated partly by FAK, the role of FAK in neutrophil transmigration was examined using two complementary methods. siRNA was used to down‐regulate total FAK protein while dominant‐negative,... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619510 Mon, 23 Jan 2012 11:21:37 +0100 5619510 http://www.medworm.com/index.php?rid=5619509&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142342 AbstractA major focus of researchers studying leukocyte recruitment has been to identify and understand how cell surface endothelial adhesion molecules, cell‐to‐cell junctional protein complexes, secreted chemokines and chemoattractants, and the vessel basement membrane structure organization coordinate the process of leukocyte recruitment. As research expands beyond the components initially identified as being necessary for leukocyte recruitment, attention has turned to the structures that regulate endothelial cell‐to‐matrix adhesion. In this issue of the European Journal of Immunology, Parsons et al. [Eur. J. Immunol. 2012. 42: 436–446] identify new players in the regulation of neutrophil diapedesis (transendothelial migration), namely the focal adhesion proteins, paxillin and ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619509 Mon, 23 Jan 2012 11:21:17 +0100 5619509 http://www.medworm.com/index.php?rid=5619508&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142337 AbstractThe field of vaccine adjuvants has been an area of active research and development because of the need to improve the generation of protective immunity to a large number of pathogens, as well as in diseases such as cancer. Adjuvants can also help induce stronger immune responses with fewer injections, and consequently improve both the feasibility and success rate of large‐scale population vaccine campaigns in developing countries. A current challenge is to identify vaccine adjuvants of various classes (cytokines, toll‐like receptor ligands, etc.) with specific immune‐modulating properties in order to tailor the immune response to certain pathological situations. In this issue, Van Roey et al. [Eur. J. Immunol. 2012. 42: 353–363] explore one of these challenges, namely to id... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619508 Mon, 23 Jan 2012 11:21:16 +0100 5619508 http://www.medworm.com/index.php?rid=5619507&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201290003 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619507 Mon, 23 Jan 2012 11:21:12 +0100 5619507 http://www.medworm.com/index.php?rid=5619506&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201290002 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619506 Mon, 23 Jan 2012 11:21:10 +0100 5619506 http://www.medworm.com/index.php?rid=5619505&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201290001 AbstractCover imageThe cover is based on a spinal cord histology section taken from a TNFR2−/− mouse adoptively transferred with TNFR2−/− Treg cells prior to immunization with MOG35–55 to induce EAE. The section is stained with Luxol Fast blue to detect demyelination; Luxol Fast Red, which detects inflammatory infiltration, is the counterstain. The image is taken from the article by Tsakiri et al. (pp. 403–412) in which it is shown that TNFR2 on non‐haematopoietic cells is necessary for Treg‐cell suppressive activity and repression of EAE development. The colour of the image has been digitally altered for the cover.CMV: Fine tuning the NK‐cell response during chronic hepatitis infectionTwo recent studies reported on the expansion of NKG2C+ NK cells during chronic hepatiti... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619505 Mon, 23 Jan 2012 11:21:09 +0100 5619505 http://www.medworm.com/index.php?rid=5619504&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201290000 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619504 Mon, 23 Jan 2012 11:21:07 +0100 5619504 http://www.medworm.com/index.php?rid=5619503&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201290005 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619503 Mon, 23 Jan 2012 11:21:06 +0100 5619503 http://www.medworm.com/index.php?rid=5619502&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201290004 AbstractThe cover is based on a spinal cord histology section taken from a TNFR2−/− mouse adoptively transferred with TNFR2−/− Treg cells prior to immunization with MOG35–55 to induce EAE. The section is stained with Luxol Fast blue to detect demyelination; Luxol Fast Red, which detects inflammatory infiltration, is the counterstain. The image is taken from the article by Tsakiri et al. (pp. 403–412) in which it is shown that TNFR2 on non‐haematopoietic cells is necessary for Treg‐cell suppressive activity and repression of EAE development. The colour of the image has been digitally altered for the cover. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619502 Mon, 23 Jan 2012 11:21:04 +0100 5619502 http://www.medworm.com/index.php?rid=5624678&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22259035%26dopt%3DAbstract Death receptor 3 is essential for generating optimal protective CD4(+) T-cell immunity against Salmonella. Eur J Immunol. 2012 Jan 19; Authors: Buchan SL, Taraban VY, Slebioda TJ, James S, Cunningham AF, Al-Shamkhani A Abstract The TNF receptor superfamily member death receptor 3 (DR3) exacerbates Th2- and Th17-cell-mediated inflammatory and autoimmune conditions, yet no role in host defence has been reported. Here, we examined the role of DR3 during infection with Salmonella enterica serovar Typhimurium. Infection resulted in protracted expression of the DR3 ligand TL1A but not the related TNF superfamily proteins OX40L or CD30L. TL1A expression was localized to splenic F4/80(+) macrophages where S. enterica Typhimurium replicates, and temporally coincided with the onset o... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5624678 Thu, 19 Jan 2012 05:00:00 +0100 5624678 http://www.medworm.com/index.php?rid=5607712&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201041950 AbstractThe TNF receptor superfamily member death receptor 3 (DR3) exacerbates Th2‐ and Th17‐cell‐mediated inflammatory and autoimmune conditions, yet no role in host defence has been reported. Here, we examined the role of DR3 during infection with Salmonella enterica serovar Typhimurium. Infection resulted in protracted expression of the DR3 ligand TL1A but not the related TNF superfamily proteins OX40L or CD30L. TL1A expression was localized to splenic F4/80+ macrophages where S. enterica Typhimurium replicates, and temporally coincided with the onset of CD4+‐cell expansion. To address the relevance of the TL1A‐DR3 interaction, we examined immune responses to S. enterica Typhimurium in mice lacking DR3. Infected DR3−/− mice harboured reduced numbers of antigen‐experience... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5607712 Thu, 19 Jan 2012 05:00:00 +0100 5607712 http://www.medworm.com/index.php?rid=5596684&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141969 Cell survival transcription factor FOXO3 has been recently implicated in moderating pro‐inflammatory cytokine production by dendritic cells (DCs), but the molecular mechanisms are unclear. It was suggested that FOXO3 could antagonise NF‐κB activity, while IKKβ was demonstrated to inactivate FOXO3, suggesting a cross‐talk between the two pathways. Therefore, FOXO3 activity must be tightly regulated to allow for an appropriate inflammatory response. Here we show that in human monocyte derived DCs (MDDCs), FOXO3 is able to antagonise signalling intermediates downstream of the Toll like receptor (TLR) 4, such as NF‐κB and Interferon Regulatory Factors (IRFs), resulting in inhibition of interferon (IFN)‐β expression. We also demonstrate that activity of FOXO3 itself is regulated b... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5596684 Tue, 17 Jan 2012 05:00:00 +0100 5596684 http://www.medworm.com/index.php?rid=5580548&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142223 AbstractEctoenzymes are a diverse group of membrane proteins that have their catalytic sites outside the plasma membrane. Many of them are found on leukocytes and endothelial cells, and they are multifunctional in nature. Collectively, different ectoenzymes can modulate each step of leukocyte–endothelial contacts, as well as subsequent cell migration in tissues. Here, we review how ectoenzymes belonging to the oxidase, NAD‐metabolizing enzyme, nucleotidase and peptidase/protease families regulate and fine‐tune leukocyte trafficking, and how ectoenzymes have been targeted both in preclinical and clinical trials. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5580548 Tue, 10 Jan 2012 05:00:00 +0100 5580548 http://www.medworm.com/index.php?rid=5571752&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142193 The altered expression of transcription factors in hematopoietic stem cells and their subsequent lineages can alter the development of lymphoid and myeloid lineages. The role of the transcriptional repressor Snai3 protein in the derivation of cells of the hematopoietic system was investigated. Snai3 is expressed in terminal T‐cell and myeloid lineages therefore we chose to determine if expressing Snai3 in the early stages of hematopoietic development would influence cell lineage determination. Expression of Snai3 by retroviral transduction of hematopoietic stem cells using bone marrow chimera studies demonstrated a block in lymphoid cell development and enhanced expansion of myeloid lineage cells. Analysis of Snai3 expressing hematopoietic precursor cells showed normal numbers of immatur... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571752 Wed, 04 Jan 2012 05:00:00 +0100 5571752 http://www.medworm.com/index.php?rid=5571751&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141657 Although periodontal tissue is continually challenged by microbial plaque, it is generally maintained in a healthy state. To understand the basis for this, we investigated innate antiviral immunity in human periodontal tissue. The expression of mRNA encoding different antiviral proteins, myxovirus resistance A (MxA), protein kinase R (PKR), oligoadenylate synthetase (OAS), and secretory leukocyte protease inhibitor (SLPI) were detected in both healthy tissue and that with periodontitis. Immunostaining data consistently showed higher MxA protein expression in the epithelial layer of healthy gingiva as compared with tissue with periodontitis. Human MxA is thought to be induced by type I and III IFNs but neither cytokine type was detected in healthy periodontal tissues. Treatment in vitro of ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571751 Wed, 04 Jan 2012 05:00:00 +0100 5571751 http://www.medworm.com/index.php?rid=5571750&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141613 Increasing evidence suggests that antibodies can have stimulatory effects on T‐cell immunity. However, the contribution of circulating antigen‐specific antibodies on MHC class I cross‐priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross‐presentation of antigen to CD8+ T cells. Mice with hapten‐specific circulating antibodies, but naïve for the T‐cell antigen, were infused with haptenated antigen and CD8+ T‐cell induction was measured. Mice with circulating hapten‐specific antibodies showed significantly enhanced cross‐presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross‐presentation in mice with circulating antigen‐specific antibodies was associated with... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571750 Wed, 04 Jan 2012 05:00:00 +0100 5571750 http://www.medworm.com/index.php?rid=5571749&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141958 Epidermal Langerhans cells (LCs) are dendritic APCs that play an important role in cutaneous immune responses. LCs are associated with epidermal nerves and the neuropeptides vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP) inhibit LC Ag presentation for Th1‐type immune responses. Here we examined whether PACAP or VIP modulates LC Ag presentation for induction of IL‐17A‐producing CD4+ T cells. Treatment with VIP or PACAP prior to in vitro LC Ag presentation to CD4+ T cells enhanced IL‐17A, IL‐6 and IL‐4 production, decreased IFN‐γ and IL‐22 release and increased RORγt and Gata3 mRNA expression while decreasing T‐bet expression. The CD4+ T‐cell population was increased in IL‐17A‐ and IL‐4‐expressing cells a... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571749 Wed, 04 Jan 2012 05:00:00 +0100 5571749 http://www.medworm.com/index.php?rid=5571748&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141907 CD16+ monocytes have unique features with respect to phenotype and function. We have used transcriptional profiling for comparison of CD16+ monocytes and classical monocytes. We show herein that 187 genes are greater than five‐fold differentially expressed, including 90 genes relevant to immune response and inflammation. Hierarchical clustering of data for monocyte subsets and CD1c+ myeloid blood dendritic cells (DCs) demonstrate that CD16+ cells are more closely related to classical monocytes than to DCs.RT‐PCR for ten genes with the strongest differential expression confirmed the pattern including a lower mRNA level for CD14, CD163 and versican in CD16+ monocytes. The pattern was similar for CD16+ monocytes at rest and after exercise mobilization from the marginal pool. By contrast, ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571748 Wed, 04 Jan 2012 05:00:00 +0100 5571748 http://www.medworm.com/index.php?rid=5571747&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141965 Gastrointestinal inflammation is mediated by the pro‐inflammatory mediators interleukin‐8 (IL‐8) and prostaglandin E2 (PGE2). PGE2 binding and coupling through EP2/4 receptor subtypes on colonic epithelial cells stimulates cyclic AMP and IL‐8 production. Here we determined the mechanisms whereby PGE2 regulates IL‐8 in Caco2 colonic epithelial cells and in cells over expressing EP2/4 receptors. PGE2 coupling through EP2 activated the transcription factor inducible cAMP early repressor (ICER) whereas coupling through EP4 receptors activated the cyclic AMP‐responsive element‐binding protein (CREB). Activation of CREB in Caco2/EP2S was PKA dependent, whereas in EP4S cells, activation of CREB occurred through the PKA and PI3K pathways. Since ICER lacks the trans‐activation domai... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571747 Wed, 04 Jan 2012 05:00:00 +0100 5571747 http://www.medworm.com/index.php?rid=5571746&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201041286 Cytohesin 1 Interacting protein (Cytip) is induced during DC maturation and in T cells upon activation. It has also been shown to be involved in the regulation of immune responses. Here, we evaluated the functional consequences of Cytip deficiency in DCs using Cytip KO mice. No difference in DC subpopulations in the skin draining lymph nodes was found between Cytip KO mice and their WT counterparts, excluding a role in DC development. To investigate the function of Cytip in DCs in vivo, we used TNCB‐induced contact hypersensitivity (CHS) as a model system. In the sensitisation as well as in the elicitation phase, DCs derived from Cytip KO mice induced an increased inflammatory reaction indicated by more pronounced ear swelling. Furthermore, IL‐12 production was increased in Cytip KO BM... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571746 Wed, 04 Jan 2012 05:00:00 +0100 5571746 http://www.medworm.com/index.php?rid=5571745&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141519 In this study, we report that mouse peritoneal cavity (PerC) B cells demonstrate in vivo and in vitro phagocytic activities for Staphylococcus aureus, Escherichia coli and polystyrene fluorescent microspheres. Approximately 5% of PerC B cells, mainly B1b cells, showed phagocytic activity. Ingested microbes were killed efficiently in the phagolysosome. The antigen‐specific B‐cell antigen receptor (BCR) promoted B‐cell phagocytosis, resulting in antigen presentation to T cells after uptake of bacteria. Our results reveal for the first time that mouse B1 cells have active phagocytic capabilities and thereby act as a bridge linking innate and adaptive immunity. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571745 Wed, 04 Jan 2012 05:00:00 +0100 5571745 http://www.medworm.com/index.php?rid=5571744&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141511 Short‐lived protein translation products are proposed to be a major source of substrates for MHC class I antigen processing and presentation; however, a direct link between protein stability and the presentation level of MHC class I–peptide complexes has not been made. We have recently discovered that the peptide Tyr(369‐377), derived from the tyrosinase protein, is highly presented by HLA‐A2 on the surface of melanoma cells. To examine the molecular mechanisms responsible for this presentation, we compared characteristics of tyrosinase in melanoma cell lines that present high or low levels of HLA‐A2‐Tyr(369‐377) complexes. We found no correlation between mRNA levels and the levels of HLA‐A2‐Tyr(369‐377) presentation. Co‐localization experiments revealed that in cell ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571744 Wed, 04 Jan 2012 05:00:00 +0100 5571744 http://www.medworm.com/index.php?rid=5571743&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141786 The receptor activator of NFkB (RANK) is especially well‐studied in the context of bone remodelling, and RANK and its ligand, RANKL, are key molecules in the induction of bone resorbing osteoclasts. We now report that polymorphonuclear neutrophils (PMNs) contain preformed RANK, stored in secretory vesicles and in the specific granules. Upon stimulation of PMNs in vitro, RANK was translocated to the cell membrane. In patients with persistent bacterial infections, RANK surface expression was enhanced compared with that of healthy individuals. The functional activity of RANK was assessed by determining migration of PMNs towards RANKL. A time‐and dose dependent migration was seen, leading to the conclusion that RANK on PMNs is functional. We presume that a regulated RANK expression contrib... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571743 Wed, 04 Jan 2012 05:00:00 +0100 5571743 http://www.medworm.com/index.php?rid=5571742&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142045 Plasmacytoid DCs (pDCs) are the professional interferon (IFN)‐producing cells of the immune system. pDCs specifically express TLR7 and TLR9 molecules and produce massive amounts of type I IFN by sensing microbial nucleic acids via TLR7 and TLR9. Here we report that PACSIN1, a member of the protein kinase C and casein kinase substrate in neurons (PACSINs) family, is specifically expressed in human and mouse pDCs. Knockdown of PACSIN1 by shRNA in a human pDC cell line significantly inhibited the type 1 IFN response of the pDCs to TLR9 ligand. PACSIN1‐deficient mice exhibited normal levels of conventional DCs and pDCs, demonstrating that development of pDCs was intact although PACSIN1‐deficient pDCs showed reduced levels of IFN‐α production in response to both CpG‐ODN and virus. In... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571742 Wed, 04 Jan 2012 05:00:00 +0100 5571742 http://www.medworm.com/index.php?rid=5571741&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141856 The impact of cigarette smoke (CS), a risk factor for rheumatoid arthritis (RA), on autoantibody production was studied in humans and mice with and without chronic lung disease (LD). Rheumatoid factor (RF), anti‐cyclic citrullinated peptides (CCP) and anti‐HSP70 autoantibodies were measured in several mouse strains and in cohorts of smokers and non‐smokers with and without autoimmune disease. Chronic smoking induced RFs in AKR/J mice, which are most susceptible to LD. RFs were identified in human smokers, preferentially in those with LD. Anti‐HSP70 autoantibodies were identified in CS‐exposed AKR/J mice but not in ambient air exposed AKR/J controls. Whereas inflammation could induce anti‐HSP70 IgM, smoke exposure promoted the switch to anti‐HSP70 IgG autoantibodies. Elevated ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571741 Wed, 04 Jan 2012 05:00:00 +0100 5571741 http://www.medworm.com/index.php?rid=5571740&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201041225 A vaccine protecting against all influenza strains is a long‐sought goal, particularly for emerging pandemics. As previously shown, vaccines based on the highly conserved extracellular domain of M2 (M2e) may protect against all influenza A strains. Here we demonstrate that M2e‐specific monoclonal antibodies (mAbs) protect mice from a lethal influenza infection. To be protective, antibodies had to be able to bind to Fc receptors and fix complement. Furthermore, mAbs of IgG2c isotype were protective in mice, while antibodies of identical specificity, but of the IgG1 isotype, failed to prevent disease. These findings readily translated into vaccine design. A vaccine targeting M2 in the absence of a toll‐like receptor (TLR) 7 ligand primarily induced IgG1, whilst the same vaccine linked ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571740 Wed, 04 Jan 2012 05:00:00 +0100 5571740 http://www.medworm.com/index.php?rid=5571739&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141442 During hematopoietic lineage development, HSCs sequentially commit towards myeloid or lymphoid lineages in a tightly regulated manner, which under normal circumstances is irreversible. However, studies have established that targeted deletion of the B‐lineage‐specific transcription factor, paired box gene 5 (Pax5), enables B cells to differentiate towards other hematopoietic lineages, in addition to generating progenitor B‐cell lymphomas. Our previous studies showed that subversion of PKCα in developing B cells transforms B‐lineage cells. Here we demonstrate that PKCα modulation in committed CD19+ B‐lymphocytes also promoted lineage conversion towards myeloid, NK‐ and T‐cell lineages upon Notch ligation. This occurred via a reduction in Pax5 expression resulting from a downr... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571739 Wed, 04 Jan 2012 05:00:00 +0100 5571739 http://www.medworm.com/index.php?rid=5571738&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142057 In this study, we report that in humans an activated complement system mainly augments Candida albicans‐induced host pro‐inflammatory cytokine production via C5a‐C5a receptor signaling, while phagocytosis and intracellular killing of Candida are not influenced. By blocking the C5a‐C5aR signaling pathway, either with anti‐C5a antagonist antibodies or with the C5aR antagonist W‐54001, C. albicans‐induced IL‐6 and IL‐1β levels were significantly reduced. Recombinant C5a augmented cytokine production. In addition, using serum from patients with various complement deficiencies, we demonstrated a crucial role of C5, but not C6 or the membrane attack complex, in C. albicans‐induced IL‐6 and IL‐1β production in monocytes. These findings reveal a central role of anaphylato... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571738 Wed, 04 Jan 2012 05:00:00 +0100 5571738 http://www.medworm.com/index.php?rid=5571737&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142086 DCs sense the microenvironment through several types of receptors recognizing pathogen‐associated‐molecular patterns. In particular, C‐type lectins, expressed by distinct subsets of DCs, recognise and internalize specific carbohydrate antigen in a Ca2+‐dependent manner. Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC‐based anticancer immunotherapy. Here we investigated the role of the macrophage galactose type C‐lectin receptor (MGL), expressed by immature (i) DCs, as a molecular target for GalNAc (Tn)‐carrying tumor‐associated antigens to improve DC performance.MGL expressed by ex vivo‐generated iDCs from healthy donors was engaged by a 60‐mer MUC1 9Tn‐glycopeptide as a Tn‐carrying TAA, and an anti‐MGL antibody, as a sp... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571737 Wed, 04 Jan 2012 05:00:00 +0100 5571737 http://www.medworm.com/index.php?rid=5571736&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141857 Antigen affinity is commonly viewed as the driving force behind the selection for dominant clonotypes that can occur during the T cell‐dependent processes of class switch recombination (CSR) and immune maturation. To test this view, we analyzed the variable gene repertoires of natural monoclonal antibodies to the hapten 2‐phenyloxazolone (phOx) as well as those generated after phOx protein carrier‐induced thymus‐dependent or Ficoll‐induced thymus independent antigen stimulation. In contrast to expectations, the extent of IgM heterogeneity proved similar and many IgM from these three populations exhibited similar or even greater affinities than the classic Ox1 clonotype that dominates only after CSR among primary and memory IgG. The population of clones that were selected during C... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571736 Wed, 04 Jan 2012 05:00:00 +0100 5571736 http://www.medworm.com/index.php?rid=5571735&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141835 Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system. Current therapies decrease the frequency of relapses and limit, to some extent, but do not prevent disease progression. Hence, new therapeutic approaches that modify the natural course of MS need to be identified. Tolerance induction to self‐antigens using monocyte‐derived dendritic cells (MDDCs) is a promising therapeutic strategy in autoimmunity. In this work we sought to generate and characterize tolerogenic MDDCs (tolDCs) from relapsing‐remitting (RR) MS patients, loaded with myelin peptides as specific antigen, with the aim of developing immunotherapeutics for MS. MDDCs were generated from both healthy‐blood donors and RR‐MS patients, and MDDC maturation was induced with a pr... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571735 Wed, 04 Jan 2012 05:00:00 +0100 5571735 http://www.medworm.com/index.php?rid=5571734&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142071 We have investigated the role of CD40 signaling in islet‐reactive, diabetogenic CD4+ Th1 T‐cell clones. Using multispectral flow cytometry, we showed that CD40 and CD154 are co‐expressed and form complexes on the surface of activated T cells. We also demonstrate that activated T cells can transactivate CD4+CD40+ T cells through the CD40‐CD154 pathway. To investigate the role of CD40 signaling on Th1 cells, we used the diabetogenic clone BDC‐5.2.9 retrovirally transduced with a truncated form of the CD40 molecule to produce a CD40 dominant‐negative T‐cell clone. Upon challenge with antigen in vitro, the production of IFN‐γ by BDC‐5.2.9 CD40DN was greatly reduced and in vivo, the dominant‐negative variant was unable to induce diabetes. Transduction with the CD40DN vector... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571734 Wed, 04 Jan 2012 05:00:00 +0100 5571734 http://www.medworm.com/index.php?rid=5596683&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141690 T‐cell activation and the subsequent transformation of activated T cells into T‐cell blasts require profound changes in cell volume. However, the impact of cell volume regulation for T‐cell immunology has not been characterized. Here we studied the role of the cell‐volume regulating osmolyte transporter Taut for T‐cell activation in Taut‐deficient mice. T‐cell mediated recall responses were severely impaired in taut−/− mice as shown with B16 melanoma rejection and hapten‐induced contact hypersensitivity. CD4+ and CD8+ T cells were unequivocally located within peripheral lymph nodes of unprimed taut−/− mice but significantly decreased in taut−/− compared with taut+/+ mice following in vivo activation. Further analysis revealed that Taut is critical for rescuing T... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5596683 Sun, 01 Jan 2012 05:00:00 +0100 5596683 http://www.medworm.com/index.php?rid=5580547&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142231 AbstractChemokines are proinflammatory mediators that regulate leukocyte trafficking at different steps of the leukocyte recruitment cascade. Studies using new imaging approaches and new mouse models are giving new insights into the role of chemokines in neutrophil migration at sites of inflammation. Conventional rolling and adhesion paradigms as well as previously unappreciated functions of signaling pathways triggering leukocyte adhesion, intralumenal crawling and transendothelial migration are compiled and described here. In this review we will summarize recent work in this field, highlighting in vivo imaging studies that examine the behavior of neutrophils in response to chemokines. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5580547 Sun, 01 Jan 2012 05:00:00 +0100 5580547 http://www.medworm.com/index.php?rid=5578879&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22213041%26dopt%3DAbstract Authors: Abstract COVER IMAGE: The cover shows a histological analysis of an ear section from a C57BL/6 mouse that was first sensitised with 2,4-dinitrofluorobenzene on the belly and then challenged 4 days later with 2,4-dinitrofluorobenzene on the ear. Haematoxylin and eosin staining shows massive skin infiltration by mononuclear cells and granulocytes 24 h after challenge. The image is from Rouzaire et al. (pp. 80-88) in which the authors show that NK cells and T cells induce different types of inflammatory reactions in the skin during recall responses to haptens; of note, NK cell-mediated pathogenesis does not rely on cellular infiltrate. A 'MÉNAGE À TROIS' IN THE GERMINAL CENTRE INVOLVING HUMAN ΓΔ T CELLS: Vγ9/Vδ2 T cells comprise a minor subset of unconventional T cells... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5578879 Sun, 01 Jan 2012 05:00:00 +0100 5578879 http://www.medworm.com/index.php?rid=5578878&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22213042%26dopt%3DAbstract Authors: Cossarizza A, Radbruch A PMID: 22213042 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5578878 Sun, 01 Jan 2012 05:00:00 +0100 5578878 http://www.medworm.com/index.php?rid=5578877&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22213043%26dopt%3DAbstract Authors: Raes G, De Baetselier P, Van Ginderachter JA PMID: 22213043 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5578877 Sun, 01 Jan 2012 05:00:00 +0100 5578877 http://www.medworm.com/index.php?rid=5578876&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22213044%26dopt%3DAbstract Authors: Lutz MB Abstract The hematopoietic growth factor GM-CSF has long been known for its colony-formation properties in the generation of neutrophils, macrophages and DCs. However, a study by Miah et al. in this issue of the European Journal of Immunology [Eur. J. Immunol. 2012. 42: 58-68] reports that GM-CSF also terminates its own proliferation-inducing STAT5-signaling via induction of the SOCS family member cytokine-inducible SH2-domain protein (CISH, also known as CIS). CISH levels were continuously increased during murine GM-CSF-dependent DC development in vitro and CISH, in turn, suppressed STAT5 phosphorylation to inhibit further GM-CSF signals. In addition, CISH activity promoted MHC class I- but not MHC class II-dependent antigen presentation after DC maturation, selec... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5578876 Sun, 01 Jan 2012 05:00:00 +0100 5578876 http://www.medworm.com/index.php?rid=5578875&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22213045%26dopt%3DAbstract Authors: Holmdahl R, Malissen B Abstract The dramatic increase in the amount of research data being produced necessarily leads to higher demands on statistical thresholds and on experimental planning. This is to avoid positive selection of multiple tested data. Here we would like to highlight the need for including littermate controls in animal experiments, in particular when genetically modified strains are analysed for quantitative phenotypes. Thus, this suggestion will have impact on most immunological experiments performed today. PMID: 22213045 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5578875 Sun, 01 Jan 2012 05:00:00 +0100 5578875 http://www.medworm.com/index.php?rid=5578874&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22213046%26dopt%3DAbstract Authors: PMID: 22213046 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5578874 Sun, 01 Jan 2012 05:00:00 +0100 5578874 http://www.medworm.com/index.php?rid=5578873&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22213047%26dopt%3DAbstract Authors: Rouzaire P, Luci C, Blasco E, Bienvenu J, Walzer T, Nicolas JF, Hennino A Abstract The cover shows a histological analysis of an ear section from a C57BL/6 mouse that was first sensitised with 2,4-dinitrofluorobenzene on the belly and then challenged 4 days later with 2,4-dinitrofluorobenzene on the ear. Haematoxylin and eosin staining shows massive skin infiltration by mononuclear cells and granulocytes 24 h after challenge. The image is from Rouzaire et al. (pp. 80-88) in which the authors show that NK cells and T cells induce different types of inflammatory reactions in the skin during recall responses to haptens; of note, NK cell-mediated pathogenesis does not rely on cellular infiltrate. PMID: 22213047 [PubMed - in process] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5578873 Sun, 01 Jan 2012 05:00:00 +0100 5578873 http://www.medworm.com/index.php?rid=5571733&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142105 In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5571733 Sun, 01 Jan 2012 05:00:00 +0100 5571733 http://www.medworm.com/index.php?rid=5551809&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142048 AbstractThe dramatic increase in the amount of research data being produced necessarily leads to higher demands on statistical thresholds and on experimental planning. This is to avoid positive selection of multiple tested data. Here we would like to highlight the need for including littermate controls in animal experiments, in particular when genetically modified strains are analysed for quantitative phenotypes. Thus, this suggestion will have impact on most immunological experiments performed today. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551809 Fri, 30 Dec 2011 23:53:42 +0100 5551809 http://www.medworm.com/index.php?rid=5551808&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142271 AbstractThe hematopoietic growth factor GM‐CSF has long been known for its colony‐formation properties in the generation of neutrophils, macrophages and DCs. However, a study by Miah et al. in this issue of the European Journal of Immunology[Eur. J. Immunol. 2012. 42: 58–68] reports that GM‐CSF also terminates its own proliferation‐inducing STAT5‐signaling via induction of the SOCS family member cytokine‐inducible SH2‐domain protein (CISH, also known as CIS). CISH levels were continuously increased during murine GM‐CSF‐dependent DC development in vitro and CISH, in turn, suppressed STAT5 phosphorylation to inhibit further GM‐CSF signals. In addition, CISH activity promoted MHC class I‐ but not MHC class II‐dependent antigen presentation after DC maturation, select... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551808 Fri, 30 Dec 2011 23:53:39 +0100 5551808 http://www.medworm.com/index.php?rid=5551807&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190081 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551807 Fri, 30 Dec 2011 23:53:35 +0100 5551807 http://www.medworm.com/index.php?rid=5551806&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190083 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551806 Fri, 30 Dec 2011 23:53:33 +0100 5551806 http://www.medworm.com/index.php?rid=5551805&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190082 AbstractCover imageThe cover shows a histological analysis of an ear section from a C57BL/6 mouse that was first sensitised with 2,4‐dinitrofluorobenzene on the belly and then challenged 4 days later with 2,4‐dinitrofluorobenzene on the ear. Haematoxylin and eosin staining shows massive skin infiltration by mononuclear cells and granulocytes 24 h after challenge. The image is from Rouzaire et al. (pp. 80–88) in which the authors show that NK cells and T cells induce different types of inflammatory reactions in the skin during recall responses to haptens; of note, NK cell‐mediated pathogenesis does not rely on cellular infiltrate.A ‘ménage à trois’ in the germinal centre involving human γδ T cellsVγ9/Vδ2 T cells comprise a minor subset of unconventional T cells in the bloo... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551805 Fri, 30 Dec 2011 23:53:32 +0100 5551805 http://www.medworm.com/index.php?rid=5551804&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190080 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551804 Fri, 30 Dec 2011 23:53:31 +0100 5551804 http://www.medworm.com/index.php?rid=5551803&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190085 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551803 Fri, 30 Dec 2011 23:53:30 +0100 5551803 http://www.medworm.com/index.php?rid=5551802&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190084 AbstractThe cover shows a histological analysis of an ear section from a C57BL/6 mouse that was first sensitised with 2,4‐dinitrofluorobenzene on the belly and then challenged 4 days later with 2,4‐dinitrofluorobenzene on the ear. Haematoxylin and eosin staining shows massive skin infiltration by mononuclear cells and granulocytes 24 h after challenge. The image is from Rouzaire et al. (pp. 80–88) in which the authors show that NK cells and T cells induce different types of inflammatory reactions in the skin during recall responses to haptens; of note, NK cell‐mediated pathogenesis does not rely on cellular infiltrate. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5551802 Fri, 30 Dec 2011 23:53:28 +0100 5551802 http://www.medworm.com/index.php?rid=5550877&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fsites%2Fentrez%3Fcmd%3DSearch%26db%3Dpubmed%26term%3D%28%28%28Eur%2520J%2520Immunol%29%2520AND%2520%25222011%252F11%252F19%252006.24%2522%255BMHDA%255D%253A%25222011%252F12%252F30%252006.12%2522%255BMHDA%255D%29%29%2520NOT%2520%28%28%2520%28%28%28%2522Eur%2520J%2520Immunol%2522%255BTIAB%255D%29%29%29%2520AND%2520%25220001%2522%255BEDAT%255D%253A%25222011%252F11%252F19%252006.24%2522%255BEDAT%255D%29%29 149 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Eur J Immunol These pubmed results were generated on 2011/12/30PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5550877 Fri, 30 Dec 2011 11:12:03 +0100 5550877 http://www.medworm.com/index.php?rid=5543835&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141754 AbstractWhether or not allorestriction should be distinguished from alloreactivity depends on one's model of the TCR–ligand interaction. If the ligand is viewed as a determinant formed by a meld between peptide and the MHC‐encoded restricting element, then the TCR, like the BCR, has a single combining site specific for the composite epitope (the Centric Model). If, however, one views the recognition of peptide and the MHC‐encoded restricting element as independent, then interactions at two sites of the TCR must be integrated to signal the T cell (the Tritope Model). As TCR recognition of the MHC‐encoded restricting element is, by definition, restricted (allele‐specific), then under the Centric Model, all TCR signaling interactions with the composite epitope are due to allorestric... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5543835 Tue, 27 Dec 2011 05:00:00 +0100 5543835 http://www.medworm.com/index.php?rid=5619501&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141983 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619501 Fri, 23 Dec 2011 05:00:00 +0100 5619501 http://www.medworm.com/index.php?rid=5607711&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141991 AbstractIn areas where polyparasitism is highly prevalent, the impact of multiple parasites on the host response is underestimated. In particular, the presence of helminth infection coincident with malaria profoundly alters the production of malaria‐specific IFN‐γ, IL‐12p70, CXCL9, CXCL10 and CXCL11, cytokines/chemokines known to be critical in mediating malaria‐specific immunity. In order to elucidate the mechanisms underlying the suppression of malaria‐specific cytokines/chemokines, we assessed the expression of malaria‐specific IL‐12Rβ1, IL‐12Rβ2 and interferon regulatory factor (IRF)‐1 in blood obtained from 18 filaria‐infected (Fil+) and 17 filaria‐uninfected (Fil−) individuals in a filaria–malaria co‐endemic region of Mali. We found that Fil+ individual... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5607711 Fri, 23 Dec 2011 05:00:00 +0100 5607711 http://www.medworm.com/index.php?rid=5607710&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142024 AbstractNegative selection plays a key role in the clonal deletion of autoreactive T cells in the thymus. However, negative selection is incomplete; as high numbers of autoreactive T cells can be detected in normal individuals, mechanisms that regulate negative selection must exist. In this regard, we previously reported that CD24, a GPI‐anchored glycoprotein, is required for thymic generation of autoreactive T lymphocytes. The CD24‐deficient 2D2 TCR transgenic mice (2D2+CD24−/−), whose TCR recognizes myelin oligodendrocyte glycoprotein (MOG), fail to generate functional 2D2 T cells. However, it was unclear if CD24 regulated negative selection, and if so, what cellular mechanisms were involved. Here, we show that elimination of MOG or Aire gene expression in 2D2+CD24−/− mice �... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5607710 Fri, 23 Dec 2011 05:00:00 +0100 5607710 http://www.medworm.com/index.php?rid=5537261&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141983 AbstractVγ9Vδ2 γδ lymphocytes represent a T‐cell subset involved in the immune response towards pathogens and tumors. The interesting paper by Barros et al [1], and commented on by Born and O’Brien [2], has shown that these cells constitutively express CD27, a member of the TNF receptor (TNF‐R) family, and upregulate its cognate ligand, CD70, upon TCR‐engagement by γδ‐specific phosphate antigens. The resulting CD70‐CD27 interaction promoted proliferation, survival and Th1‐cell differentiation, thereby indicating that members of the TNF‐R family are critical regulators of γδ T‐cell function [1]. The study by Barros et al [1] adds to previous work highlighting a pivotal role for TNF‐TNF‐R in γδ as compared with the role in αβ lymphocytes [3]. (Source: Europe... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5537261 Fri, 23 Dec 2011 05:00:00 +0100 5537261 http://www.medworm.com/index.php?rid=5537260&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142024 AbstractNegative selection plays a key role in the clonal deletion of autoreactive T cells in the thymus. However, negative selection is incomplete; as high numbers of autoreactive T cells can be detected in normal individuals, mechanisms that regulate negative selection must exist. In this regard, we previously reported that CD24, a GPI‐anchored glycoprotein, is required for thymic generation of autoreactive T lymphocytes. The CD24‐deficient 2D2 TCR transgenic mice (2D2+CD24‐/‐), whose TCR recognizes myelin oligodendrocyte glycoprotein (MOG), fail to generate functional 2D2 T cells. However, it was unclear if the CD24 function involved regulation of negative selection, and if so, what cellular mechanisms were involved. Here we show that elimination of MOG or Aire gene expression i... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5537260 Fri, 23 Dec 2011 05:00:00 +0100 5537260 http://www.medworm.com/index.php?rid=5537259&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141921 AbstractNeutrophils play a pivotal role in the defense against bacterial, viral and fungal infections and are important mediators in the acute inflammatory response. At the same time, neutrophils are also involved in sterile inflammatory responses that are triggered by endogenous ligands. A series of immediate effector functions and the expression of proinflammatory genes enable neutrophils to initiate the immune response against the injurious agent. Among these, interleukin‐1β (IL‐1β) plays a key role in the orchestration of the inflammatory response. Induction of IL‐1β expression leads to production of cytosolic pro‐IL‐1β, which requires further processing by a proteolytic cleavage event. Caspase‐1 was initially identified as the main IL‐1β converting enzyme and the up... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5537259 Fri, 23 Dec 2011 05:00:00 +0100 5537259 http://www.medworm.com/index.php?rid=5607714&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141955 AbstractMalaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. Helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. Here we show that Strongyloides ratti, a gut‐dwelling nematode that causes transient infections, did not change the efficacy of vaccination against Plasmodium berghei. An ongoing infection with Litomosoides sigmodontis, a tissue‐dwelling filaria that induces chronic infections in BALB/c mice, significantly interfered with vaccination efficacy. The induction of P. berghei circumsporozoite protein (CSP)‐specific CD8+ T cells, achieved by a single immunization with a CSP fusion protein, was diminished in L. sigmodontis‐infected mice. This modu... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5607714 Mon, 12 Dec 2011 05:00:00 +0100 5607714 http://www.medworm.com/index.php?rid=5494350&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141651 AbstractThe suppression of inappropriate immune responses by Treg cells is one of the major ways that the body maintains immune tolerance and homeostasis. Since defects in the suppressive capacity of Treg cells underlie many different immune‐mediated diseases, there is great interest in developing ways to track the number and function of Treg cells as biomarkers of tolerance and in devising ways to enhance their function therapeutically. However, the methods of studying human Treg cells are fraught with technical challenges that can often lead to misinterpretation. The most common way to determine the suppressive capacity of human Treg cells is to measure their ability to suppress the proliferation of responding CD4+ T cells. Here, we discuss the technical considerations that must be tak... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494350 Mon, 12 Dec 2011 05:00:00 +0100 5494350 http://www.medworm.com/index.php?rid=5494343&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141955 AbstractMalaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. Helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. Here we show that Strongyloides ratti, a gut‐dwelling nematode that causes transient infections, did not change the efficacy of vaccination against Plasmodium berghei. An ongoing infection with Litomosoides sigmodontis, a tissue‐dwelling filaria that induces chronic infections in BALB/c mice, significantly interfered with vaccination efficacy. The induction of P. berghei circumsporozoite protein (CSP)‐specific CD8+ T cells, achieved by a single immunization with a CSP fusion protein, was diminished in L. sigmodontis‐infected mice. This modu... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494343 Mon, 12 Dec 2011 05:00:00 +0100 5494343 http://www.medworm.com/index.php?rid=5494342&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141902 AbstractAfter infection or vaccination, antigen‐specific T cells proliferate then contract in numbers to a memory set point. T‐cell contraction is observed after both acute and prolonged infections although it is unknown if contraction is regulated similarly in both scenarios. Here, we show that contraction of antigen‐specific CD8+ and CD4+ T cells is markedly reduced in TNF/perforin‐double deficient (DKO) mice responding to attenuated Listeria monocytogenes infection. Reduced contraction in DKO mice was associated with delayed clearance of infection and sustained T‐cell proliferation during the normal contraction interval. Mechanistically, sustained T‐cell proliferation mapped to prolonged infection in the absence of TNF, however, reduced contraction required the additional ab... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494342 Mon, 12 Dec 2011 05:00:00 +0100 5494342 http://www.medworm.com/index.php?rid=5494341&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141737 AbstractThe involvement of macrophages in Th17‐cell responses is still poorly understood. While neutrophils are thought to be the predominant effector of Th17‐cell responses, IL‐17 is also known to induce myelotropic chemokines and growth factors. Other T cell‐derived cytokines induce nonclassical functions, suggesting that IL‐17 signaling may similarly elicit unique macrophage functions. Here, we characterized the expression of subunits of the IL‐17 receptor on primary murine macrophages from different anatomical compartments. The greatest expression of IL‐17 receptors was observed on mucosal Ly6Chi “inflammatory” macrophages. We further observed upregulation of IL‐17 receptors in vitro on bone marrow‐derived macrophages in response to peptidoglycan or CpG oligonucle... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494341 Mon, 12 Dec 2011 05:00:00 +0100 5494341 http://www.medworm.com/index.php?rid=5619500&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141931 In conclusion, chronically stimulated CD8+ T cells become sensitive to PD‐1/PD‐L1‐mediated functional inhibition upon low antigen detection; a setting which is likely involved during tumor‐immune escape. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5619500 Mon, 05 Dec 2011 05:00:00 +0100 5619500 http://www.medworm.com/index.php?rid=5607713&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141930 This study indicates that the inhibitory function of HLA‐G is uncoupled from lipid raft organization, further distinguishing HLA‐G from classical HLA molecules and providing novel information in the understanding of tumor immune escape mechanism mediated through HLA‐G. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5607713 Mon, 05 Dec 2011 05:00:00 +0100 5607713 http://www.medworm.com/index.php?rid=5475927&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141581 AbstractT‐cell immunoglobulin mucin‐1 (Tim‐1) is a transmembrane protein postulated to be a key regulator of Th2‐type immune responses. This hypothesis is based in part upon genetic studies associating Tim‐1 polymorphisms in mice with a bias toward airway hyperresponsiveness (AHR) and the development of Th2‐type CD4+ T cells. Tim‐1 expressed by Th2 CD4+ T cells has been proposed to function as a co‐stimulatory molecule. Tim‐1 is also expressed by B cells, macrophages, and dendritic cells, but its role in responses by these cell types has not been firmly established. Here we generated Tim‐1 deficient mice to determine the role of Tim‐1 in a murine model of allergic airway disease that depends on the development and function of Th2 effector cells and results in the gene... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475927 Mon, 05 Dec 2011 05:00:00 +0100 5475927 http://www.medworm.com/index.php?rid=5475926&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141930 This study indicates that the inhibitory function of HLA‐G is uncoupled from lipid raft organization, further distinguishing HLA‐G from classical HLA molecules and providing novel information in the understanding of tumor immune escape mechanism mediated through HLA‐G. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475926 Mon, 05 Dec 2011 05:00:00 +0100 5475926 http://www.medworm.com/index.php?rid=5475925&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142011 AbstractHemocyanins, which boost the immune system of mammals, have been used as carrier‐adjuvants to promote antibody production against haptens and peptides, as immunostimulants during therapy for bladder carcinoma and as a component in therapeutic vaccines for cancer. These biomedical applications have led to growing interest in obtaining hemocyanins with high immunogenicity. Here, we study the immunological properties of a modified Concholepas hemocyanin (Ox‐CCH) obtained by the oxidation of its carbohydrates using sodium periodate. We assessed the internalization of Ox‐CCH into DCs and its immunogenicity and antitumor effects. Transmission electron microscopy showed no changes in Ox‐CCH quaternary structure with respect to native CCH, although proteolytic treatment followed by... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475925 Mon, 05 Dec 2011 05:00:00 +0100 5475925 http://www.medworm.com/index.php?rid=5475924&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141931 In conclusion, chronically stimulated CD8+ T cells become sensitive to PD‐1/PD‐L1 mediated functional inhibition upon low antigen detection; a setting which is likely involved during tumor immune escape. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475924 Mon, 05 Dec 2011 05:00:00 +0100 5475924 http://www.medworm.com/index.php?rid=5475923&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141702 AbstractThe abbreviations used are: DM, dorsomorphin; BMP, bone morphogenic protein; BMPR, BMP receptor; rBMP2, recombinant BMP2; rNoggin, recombinant Noggin; MAPK, mitogen‐activated protein kinase; RUNX1, runt‐related transcription factor 1; AML1, acute myeloid leukemia 1; IL‐2, interleukin‐2; Th, T helper cell; iTreg, induced regulatory T cell; ActRII, Activin type II receptor; TGF‐, transforming growth factor‐beta; IFN‐, interferon‐gamma; 7AAD, 7‐Amino‐actinomycin D; BrdU, bromodeoxyuridine; IC50, inhibitory concentration 50; CFSE, carboxyfluorescein diacetate succinimidyl ester; DN, double negative; DP, double positive; qPCR, quantitative real‐time PCR; APC, antigen‐presenting cells; DEGs, differentially expressed genes; TCR, T‐cell receptor; PDGF, platelet‐... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475923 Mon, 05 Dec 2011 05:00:00 +0100 5475923 http://www.medworm.com/index.php?rid=5475922&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141920 AbstractNK cells play an important role in tumor immunosurveillance and largely contribute to the therapeutic success of anti‐tumor antibodies like Rituximab. Here we studied the role of the TNF family member 4‐1BB ligand (4‐1BBL) during the interaction of NK cells with chronic lymphocytic leukemia (CLL) cells. 4‐1BBL was highly expressed on patient CLL B cells in all 56 investigated cases. Signaling via 4‐1BBL following interaction with 4‐1BB, which was detected on NK cells of CLL patients but not healthy individuals, led to the release of immunoregulatory cytokines including TNF by CLL cells. CLL patient sera contained elevated levels of TNF and induced 4‐1BB upregulation on NK cells, which in turn impaired direct and Rituximab‐induced NK reactivity against 4‐1BBL‐exp... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475922 Mon, 05 Dec 2011 05:00:00 +0100 5475922 http://www.medworm.com/index.php?rid=5475921&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142108 AbstractNatalizumab, an antibody against the á4 subunit of á4 integrins has been approved for multiple sclerosis (MS) therapy based on its high efficacy and safety profile. However, natalizumab has been associated with the development of progressive multifocal leukoencephalopathy (PML), a disorder caused by JC virus (JCV) infection. In order to improve our understanding of the mechanisms of action of natalizumab and to identify possible risk factors for PML development, we have characterized in detail the cell blood composition in MS patients treated with natalizumab for more than 30 months. Natalizumab induced the release of lymphoid‐ but not myeloid precursor cells, which resulted in a chronic increase of T‐, NK‐ and particularly B cells. While the percentage of recent thymic emi... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475921 Mon, 05 Dec 2011 05:00:00 +0100 5475921 http://www.medworm.com/index.php?rid=5475920&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141800 This study suggests that the choice of tumor antigens could be critical for strategies combining epigenetic drugs with immunotherapy. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475920 Mon, 05 Dec 2011 05:00:00 +0100 5475920 http://www.medworm.com/index.php?rid=5475919&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142035 We report for the first time that expression of the novel IL‐1 cytokine receptor IL‐1Rrp2 (IL‐1R6) is unique to dendritic cells (DCs) within the human myelomonocytic lineage. IL‐1Rrp2 was expressed by monocyte derived dendritic cells (MDDCs) which was dose‐dependently increased by IL‐4 and correlated with increased numbers of differentiated MDDCs. Human plasmacytoid DCs also express IL‐1Rrp2 but the receptor is not expressed by either myeloid DC type 1 (mDC1) or mDC2 cells. We also show that IL‐1F8 or IL‐1F9 cytokines, which signal through IL‐1Rrp2, induce maturation of MDDCs, as measured by increased expression of HLA‐DR and CD83 and decreased expression of CD1a. Furthermore, IL‐1F8 stimulated increased CD40 and CD80 expression and IL‐18 and IL‐12 p70 productio... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475919 Mon, 05 Dec 2011 05:00:00 +0100 5475919 http://www.medworm.com/index.php?rid=5537258&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141991 AbstractIn areas where polyparasitism is highly prevalent, the impact of multiple parasites on the host response is underestimated. In particular, the presence of helminth infection coincident with malaria profoundly alters the production of malaria‐specific IFN‐γ, IL‐12p70, CXCL9, CXCL10, AND CXCL11, cytokines/chemokines known to be critical in mediating malaria‐specific immunity. In order to elucidate the mechanisms underlying the suppression of malaria‐specific cytokines/chemokines, we assessed the expression of malaria‐specific IL‐12Rβ1, IL‐12Rβ2 and IRF‐1 in blood obtained from 18 filaria‐infected (Fil+) and 17 filaria‐uninfected (Fil–) individuals in a filaria‐malaria co‐endemic region of Mali. We found that Fil+ individuals had significantly lower RNA ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5537258 Thu, 01 Dec 2011 05:00:00 +0100 5537258 http://www.medworm.com/index.php?rid=5494340&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141910 In this study, we sought to determine whether activation of the pro‐inflammatory inhibitor of κB kinase βIKKβ canonical NF‐κB pathway promoted vaccine‐induced immune responses. An adenovirus expressing constitutively‐activated IKKβ (AdIKK) induced robust DC maturation and high expression of key cytokines compared to a control virus. In vivo, AdIKK triggered rapid inflammation after pulmonary infection, increased leukocyte entry into draining LNs, and enhanced early antibody and T‐cell responses. Notably, AdIKK did not influence the overall magnitude of the adaptive immune response. These results indicate that induction of inflammation by IKKβ/NF‐κB in this setting impacts the kinetics but not the magnitude of adaptive immune responses. These findings therefore help defin... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5494340 Thu, 01 Dec 2011 05:00:00 +0100 5494340 http://www.medworm.com/index.php?rid=5475918&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142094 AbstractDendritic cells (DCs) are the most potent type of antigen presenting cell (APC) to stimulate T cells [1, 2]. However, the modulation of antigen‐specific T‐cell responses against a variety of pathogens using different types of APCs such as DCs and monocytes has never been systematically compared. We have therefore performed a comprehensive analysis of the quantity and quality of memory CD4+ T‐cell responses directed against a variety of antigens including peptide, protein, viral, fungal and bacterial derived‐antigens following stimulation with antigen‐loaded DCs or monocytes. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5475918 Thu, 01 Dec 2011 05:00:00 +0100 5475918 http://www.medworm.com/index.php?rid=5456595&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190076 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456595 Wed, 30 Nov 2011 23:54:11 +0100 5456595 http://www.medworm.com/index.php?rid=5456594&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141453 AbstractSurvival of antigen‐specific CD8+ T cells in peripheral lymphoid organs during viral infection is known to be dependent predominantly on IL‐7 and IL‐15. However, little is known about a possible influence of tissue environmental factors on this process. To address this question, we studied survival of memory antigen‐specific CD8+ T cells in the small intestine. Here, we show that 2 months after vaccinia virus infection, B8R20–27/H2‐Kb tetramer+ CD8+ T cells in the small intestinal intraepithelial (SI‐IEL) layer are found in mice deficient in IL‐15 expression. Moreover, SI‐IEL and lamina propria lymphocytes do not express the receptor for IL‐7 (IL‐7Rα/CD127). In addition, after in vitro stimulation with B8R20–27 peptide, SI‐IEL cells do not produce high am... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456594 Wed, 30 Nov 2011 23:53:51 +0100 5456594 http://www.medworm.com/index.php?rid=5456593&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142196 AbstractLeukocyte recruitment to sites of inflammation proceeds in a cascade‐like fashion. However, it is less clear how the complex interactions among the different adhesion molecules involved in this process are coordinately regulated. A report in this issue of the European Journal of Immunology [Eur. J. Immunol. 2011. 41: 3436–3442] shows that ADAM8 may participate in the control of the adhesion molecule P‐selectin glycoprotein ligand 1. This finding suggests a new role for ADAM8 in the regulation of inflammatory processes. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456593 Wed, 30 Nov 2011 23:53:39 +0100 5456593 http://www.medworm.com/index.php?rid=5456592&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142082 This article reviews the progress made in the three decades since the recognition of AIDS and the discovery of HIV, with respect to the virus, the infected cell, and the host, as well as directions for future studies. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456592 Wed, 30 Nov 2011 23:53:36 +0100 5456592 http://www.medworm.com/index.php?rid=5456591&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190075 AbstractDiseases, such as malaria, dengue, leishmaniasis and tick‐borne encephalitis, affect a substantial percentage of the world's population and continue to result in significant morbidity and mortality. One common aspect of these diseases is that the pathogens that cause them are transmitted by the bite of an infected arthropod (e.g. mosquito, sand fly, tick). The pathogens are delivered into the skin of the mammalian host along with arthropod saliva, which contains a wide variety of bioactive molecules. These saliva components are capable of altering hemostasis and immune responses and may contribute to the ability of the pathogen to establish an infection. The biological and immunological events that occur during pathogen transmission are poorly understood but may hold the key to n... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456591 Wed, 30 Nov 2011 23:53:35 +0100 5456591 http://www.medworm.com/index.php?rid=5456590&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190074 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456590 Wed, 30 Nov 2011 23:53:34 +0100 5456590 http://www.medworm.com/index.php?rid=5456589&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190073 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456589 Wed, 30 Nov 2011 23:53:32 +0100 5456589 http://www.medworm.com/index.php?rid=5456588&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190072 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456588 Wed, 30 Nov 2011 23:53:31 +0100 5456588 http://www.medworm.com/index.php?rid=5456587&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190071 AbstractCover imageThe cover image shows immunohistological analysis of a spleen section from QMxB6 mice 96 hours after immunization with NP‐Ficoll. IgD staining (brown) determines the B‐cell follicles and NP‐staining (blue) the antibody‐producing cells; plasmablasts (dark blue regions) are present in the red pulp, and germinal centres (pale blue) can be seen in the follicles; the T zones (which lack B cells) remain unstained. The image is kindly provided by Jennifer Marshall and relates to the study Marshall et al. (pp. 3506–3512) in which it is shown that Ig class‐switch recombination during extrafollicular responses occurs at the B blast rather than the plasmablast stage.iNKT cells in diabetes: The good, The bad and the balanceInvariant natural killer T (iNKT) cells are inna... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456587 Wed, 30 Nov 2011 23:53:30 +0100 5456587 http://www.medworm.com/index.php?rid=5456586&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190070 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456586 Wed, 30 Nov 2011 23:53:28 +0100 5456586 http://www.medworm.com/index.php?rid=5456585&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190079 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456585 Wed, 30 Nov 2011 23:53:27 +0100 5456585 http://www.medworm.com/index.php?rid=5456584&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190078 (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456584 Wed, 30 Nov 2011 23:53:26 +0100 5456584 http://www.medworm.com/index.php?rid=5456583&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201190077 AbstractThe cover image shows immunohistological analysis of a spleen section from QMxB6 mice 96 hours after immunization with NP‐Ficoll. IgD staining (brown) determines the B‐cell follicles and NP‐staining (blue) the antibody‐producing cells; plasmablasts (dark blue regions) are present in the red pulp, and germinal centres (pale blue) can be seen in the follicles; the T zones (which lack B cells) remain unstained. The image is kindly provided by Jennifer Marshall and relates to the study Marshall et al. (pp. 3506–3512) in which it is shown that Ig class‐switch recombination during extrafollicular responses occurs at the B blast rather than the plasmablast stage. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456583 Wed, 30 Nov 2011 23:53:24 +0100 5456583 http://www.medworm.com/index.php?rid=5456582&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141593 AbstractHepatitis C virus (HCV) is a small, enveloped RNA virus and the number of HCV‐infected individuals worldwide is estimated to be approximately 170 million. Most HCV infections persist, with up to 80% of all cases leading to chronic hepatitis associated with liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV–host interactions have a crucial role in viral survival, persistence, pathogenicity of infection, and disease progression. Maintenance of a vigorous, sustained cellular immune response recognizing multiple epitopes is essential for viral clearance. To escape immune surveillance, HCV alters its epitopes so that they are no‐longer recognized by T cells and neutralizing antibodies, in addition to interfering with host cell cellular components and signaling pathways. ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5456582 Mon, 28 Nov 2011 05:00:00 +0100 5456582 http://www.medworm.com/index.php?rid=5449425&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141671 AbstractNo astract (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5449425 Fri, 25 Nov 2011 05:00:00 +0100 5449425 http://www.medworm.com/index.php?rid=5449424&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141915 AbstractThe major function of cytotoxic T lymphocytes (CTLs) is to eliminate pathogen‐infected and tumorigenic cells. This is mediated mainly through the exocytosis of lytic granules (LGs) containing cytotoxic components such as perforin and granzymes at the immunological synapse (IS). The soluble NSF attachment receptor (SNARE) protein isoforms are well known to be required for vesicle exocytosis in neuronal synapses, but their potential function in CTLs is only partly understood. Here we examined the expression of SNARE proteins before and after activation of primary human CD8+ T cells and determined their co‐localization with LGs and CD3 after IS formation with target cells. We found that several of the key SNARE proteins in neuronal cells were not expressed in CTLs, such as syntaxi... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5449424 Fri, 25 Nov 2011 05:00:00 +0100 5449424 http://www.medworm.com/index.php?rid=5543836&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141845 AbstractThe adoptive transfer of OVA‐specific Th1 cells into WT mice followed by OVA inhalation induces a significant elevation of airway hyper‐responsiveness (AHR) with neutrophilia but not mucus hypersecretion. Here, we demonstrate that the airway inflammation model, pathogenically characterized as severe asthma, was partly mimicked by i.n. administration of IFN‐γ. The administration of IFN‐γ instead of Th1 cells caused AHR elevation but not neutrophilia, and remarkably induced neurokinin‐2 receptor (NK2R) expression along with neurokinin A (NKA) production in the lung. To evaluate whether NKA/NK2R was involved in airway inflammation, we first investigated the role of NKA/NK2R‐signaling in airway smooth muscle cells (ASMCs) in vitro. NK2R mRNA expression was significantly a... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5543836 Tue, 22 Nov 2011 05:00:00 +0100 5543836 http://www.medworm.com/index.php?rid=5514906&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141659 AbstractThe TNF/TNFR system exerts multiple proinflammatory and immunosuppressive functions in the pathogenesis of chronic inflammation and autoimmunity. In EAE, the experimental model of Multiple Sclerosis (MS), genetic ablation of TNFR2, results in exacerbated immune reactivity and chronic disease course. The underlying mechanism driving this immunosuppressive function of TNFR2 remains unclear. We show here that chronic exacerbated EAE in TNFR2 KO mice is associated with increased Th17‐cell responses and reduced numbers of Foxp3+ Treg cells both in the spinal cord and peripheral lymphoid organs. Treg cells from TNFR2‐deficient animals developing EAE show decreased proliferative and suppressive functions, both ex vivo and in vivo, and appear responsible for the exacerbated non‐remit... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514906 Tue, 22 Nov 2011 05:00:00 +0100 5514906 http://www.medworm.com/index.php?rid=5514904&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141826 AbstractNatural killer (NK) cells are affected by infection with human cytomegalovirus (HCMV) manifested by increased expression of the HLA‐E binding activating receptor NKG2C. We here show that HCMV seropositivity was associated with a profound expansion of NKG2C+CD56dim NK cells in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Multi‐color flow cytometry revealed that the expanded NKG2C+CD56dim NK cells displayed a highly differentiated phenotype, expressed high amounts of granzyme B and exhibited polyfunctional responses (CD107a, IFN‐γ, and TNF‐α) to stimulation with antibody‐coated as well as HLA‐E expressing target cells but not when stimulated with IL‐12/IL‐18. More importantly, NKG2C+CD56dim NK cells had a clonal expression patt... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514904 Tue, 22 Nov 2011 05:00:00 +0100 5514904 http://www.medworm.com/index.php?rid=5440087&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141659 AbstractThe TNF/ TNFR system exerts multiple proinflammatory and immunosuppressive functions in the pathogenesis of chronic inflammation and autoimmunity. In EAE, the experimental model of Multiple Sclerosis (MS), genetic ablation of TNFR2, results in exacerbated immune reactivity and chronic disease course. The underlying mechanism driving this immunosuppressive function of TNFR2 remains unclear. We show here that chronic exacerbated EAE in TNFR2 KO mice is associated with increased Th17 cell responses and reduced numbers of Foxp3+ Treg cells both in the spinal cord and peripheral lymphoid organs. Treg cells from TNFR2 deficient animals developing EAE show decreased proliferative and suppressive functions, both ex vivo and in vivo, and appear responsible for the exacerbated non‐remittin... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440087 Tue, 22 Nov 2011 05:00:00 +0100 5440087 http://www.medworm.com/index.php?rid=5440086&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141748 AbstractThe role of TLR signaling to link innate and adaptive immune systems has been controversial issues remained to be resolved. Here, we determined whether MyD88‐dependent TLR signals are required for the generation of B‐cell responses during chronic Salmonella infection. Oral administration of recombinant attenuated Salmonella Typhimurium vaccine (RASV) strain in MyD88‐/‐ mice resulted in chronic infection. Infection was accompanied by enlarged germinal centers and hypergammaglobulinemia with anti‐double‐stranded DNA (dsDNA)‐specific Ab in sera, and the deposition of immune complexes in the kidneys, suggesting onset of autoimmunity. CD4+ T cells expressing PD‐1, CXCR5, ICOS, and IL‐21 were dramatically increased in chronically‐infected mice, indicating the expansio... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440086 Tue, 22 Nov 2011 05:00:00 +0100 5440086 http://www.medworm.com/index.php?rid=5440085&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141692 AbstractImmunosuppression, impaired cytokine production, and high susceptibility to secondary infections are characteristic for septic patients, and for mice after induction of polymicrobial septic peritonitis by sublethal cecal ligation and puncture (CLP). Here, we demonstrate that CLP markedly altered subsequent B‐cell responses. Total IgG and IgM levels, as well as the memory B‐cell response, were increased in septic mice, but antigen‐specific primary antibody production was strongly impaired. We found that two days after CLP, CD11b+ splenocytes were activated as demonstrated, by the increased expression of activation markers, expression of arginase, and production of NO by immature myeloid cells. The in vivo clearance of a bacterial infection was not impaired. DCs demonstrated re... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440085 Tue, 22 Nov 2011 05:00:00 +0100 5440085 http://www.medworm.com/index.php?rid=5440084&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141889 AbstractThe generation of B‐cell responses to proteins requires a functional thymus to produce CD4+ T cells which help in the activation and differentiation of B cells. Because the mature T‐cell repertoire has abundant cells with the helper phenotype, one might predict that in mature individuals the generation of B‐cell memory would proceed independently of the thymus. Contrary to that prediction, we show here that removal of the thymus after the establishment of the T‐cell compartment or sham surgery without removal of the thymus impairs the affinity maturation of antibodies. Because removal or manipulation of the thymus did not decrease the frequency of mutation of the Ig variable heavy chain exons encoding antigen‐specific antibodies, we conclude that the thymus controls affin... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440084 Tue, 22 Nov 2011 05:00:00 +0100 5440084 http://www.medworm.com/index.php?rid=5440083&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141798 AbstractIn humanized mice, the T‐cell repertoire is derived from genetically identical progenitors in distinct animals. Thus, careful comparison of the repertoires of humanized mice with repertoires of humans may reveal new aspects of the rules governing T‐cell repertoire formation. Here we performed a comprehensive assessment of the distribution of V‐J combinations of the beta chain of the T‐cell receptor (hTRBV) in NOD.SCID.c‐/‐ (NSG) humanized mice. We observed that numerous V‐J combinations were equally distributed in the thymus and in the periphery of humanized mice compared with human references. A global analysis of the data, comparing repertoire perturbation indices in humanized NSG mice and unrelated human PBMCs, reveals that 50% of the hTRBV families significantly o... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440083 Tue, 22 Nov 2011 05:00:00 +0100 5440083 http://www.medworm.com/index.php?rid=5440082&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142079 AbstractInterleukin‐1β (IL‐1β) is a pro‐inflammatory cytokine that regulates inflammatory responses to injury and infection. IL‐1β secretion requires the protease caspase‐1, which is activated following recruitment to inflammasomes. Endogenous danger associated molecular patterns (DAMPs) released from necrotic cells activate caspase‐1 through a NLRP3‐inflammasome. Here we show that the endogenous lipid metabolite sphingosine acts as a DAMP by inducing the NLRP3‐inflammasome‐dependent secretion of IL‐1β from macrophages. This process was dependent upon serine/threonine protein phosphatases since the PP1/PP2A inhibitors okadaic acid and calyculin A inhibited sphingosine‐induced IL‐1β release. IL‐1β release induced by other well characterized NLRP3‐inflammaso... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440082 Tue, 22 Nov 2011 05:00:00 +0100 5440082 http://www.medworm.com/index.php?rid=5440081&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141826 AbstractNatural killer (NK) cells are affected by infection with human cytomegalovirus (HCMV) manifested by increased expression of the HLA‐E binding activating receptor NKG2C. We here show that HCMV seropositivity was associated with a profound expansion of NKG2C+CD56dim NK cells in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Multi‐color flow cytometry revealed that the expanded NKG2C+CD56dim NK cells displayed a highly differentiated phenotype, expressed high amounts of granzyme B and exhibited polyfunctional responses (CD107a, IFN‐, and TNF‐α) to stimulation with antibody‐coated as well as HLA‐E expressing target cells but not when stimulated with IL‐12/IL‐18. More importantly, NKG2C+CD56dim NK cells had a clonal expression patter... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440081 Tue, 22 Nov 2011 05:00:00 +0100 5440081 http://www.medworm.com/index.php?rid=5440080&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141880 AbstractBiomarkers defining pathogenic effector T cells slowly have been forthcoming and towards this we identified CD4+ T cells that express CD40 (CD4+CD40+) as pathogenic in the NOD type 1 diabetes (T1D) model. CD4+CD40+ T cells rapidly and efficiently transfer T1D to NOD.scid recipients. To study the origin of CD4+CD40+ T cells and disease pathogenesis we employed a dual transgenic model expressing OVA323‐339 peptide as a neo‐self antigen on islet beta cells and medullary thymic epithelial cells (mTECs) and a transgenic TCR recognizing the OVA323‐339 peptide. CD4+CD40+ T cells and Treg cells each recognizing the cognate neo‐antigen, rather than being deleted through central tolerance, drastically expanded in the thymus. In pancreatic lymph nodes of DO11.RIPmOVA mice CD4+CD40+ T ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440080 Tue, 22 Nov 2011 05:00:00 +0100 5440080 http://www.medworm.com/index.php?rid=5440079&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141845 AbstractThe adoptive transfer of OVA‐specific Th1 cells into wild‐type mice followed by OVA inhalation induces a significant elevation of airway hyperresponsiveness (AHR) with neutrophilia but not mucus hypersecretion. Here, we demonstrate that the airway inflammation model, pathogenically characterized as severe asthma, was partly mimicked by i.n. administration of IFN‐γ. The administration of IFN‐γ instead of Th1 cells caused AHR elevation but not neutrophilia, and remarkably induced neurokinin‐2 receptor (NK2R) expression along with neurokinin A (NKA) production in the lung. To evaluate whether NKA/NK2R was involved in airway inflammation, we first investigated the role of NKA/NK2R‐signaling in airway smooth muscle cells (ASMCs) in vitro. NK2R mRNA expression was significa... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440079 Tue, 22 Nov 2011 05:00:00 +0100 5440079 http://www.medworm.com/index.php?rid=5440078&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141903 This study defines a mechanism for the protective effect of the SO2 vaccine and suggests that deletion of defined virulence networks may provide vaccine strains with potent immuno‐stimulatory properties. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440078 Tue, 22 Nov 2011 05:00:00 +0100 5440078 http://www.medworm.com/index.php?rid=5523744&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141847 AbstractHuman neonates are at significantly greater risk of serious infection than immunocompetent adults. In particular, very low birth weight infants in the neonatal intensive care nursery are at high risk of developing life‐threatening bacterial and fungal infections. Recent studies have identified Th17 cells as critical mediators of immunity to bacterial and fungal infections at epithelial barriers. Little is known, however, about the ontogeny of Th17‐cell responses in humans. The frequency of serious bacterial infections in preterm infants and the importance of Th17 cells in providing protection against such infections in animal studies prompted us to study Th17‐cell development in human neonates. Naïve CD4+ T cells from extremely preterm infants, term infants, and adults were ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5523744 Mon, 21 Nov 2011 05:00:00 +0100 5523744 http://www.medworm.com/index.php?rid=5523743&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141569 AbstractThe generation of effective type 1 T helper (Th1)‐cell responses is required for immunity against intracellular bacteria. However, some intracellular bacteria require interleukin (IL)‐17 to drive Th1‐cell immunity and subsequent protective host immunity. Here, in a model of Mycobacterium bovis Bacille Calmette–Guerin (BCG) vaccination in mice, we demonstrate that the dependence on IL‐17 to drive Th1‐cell responses is a host mechanism to overcome bacteria‐induced IL‐10 inhibitory effects. We show that BCG‐induced prostaglandin‐E2 (PGE2) promotes the production of IL‐10 which limits Th1‐cell responses, while simultaneously inducing IL‐23 and Th17‐cell differentiation. The ability of IL‐17 to downregulate IL‐10 and induce IL‐12 production allows the g... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5523743 Mon, 21 Nov 2011 05:00:00 +0100 5523743 http://www.medworm.com/index.php?rid=5523742&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141871 AbstractTumour necrosis factor alpha (TNF‐α) is a major inducer for inflammation and bone loss. Here, we investigated whether interleukin (IL)‐17 plays a role in TNF‐α‐mediated inflammation and bone resorption. Human TNF‐α transgenic (hTNFtg) mice were treated with a neutralizing anti‐IL‐17A antibody and assessed for inflammation, cartilage and bone damage. T‐cell transcription factors and lymphokine patterns were measured in the LNs. IL‐17A inhibition in the absence of IL‐1 was also evaluated by treating hTNFtg/IL‐1−/− mice with an IL‐17A neutralizing antibody. IL‐17A neutralization had only minor effects on TNF‐α‐induced inflammation but effectively reduced local and systemic bone loss by blocking osteoclast differentiation in vivo. Effects were base... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5523742 Mon, 21 Nov 2011 05:00:00 +0100 5523742 http://www.medworm.com/index.php?rid=5514907&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201041038 In this study, we investigated the potential role of CD26 in ovalbumin (OVA)‐induced airway inflammation using CD26 gene knockout mice. Compared with WT counterparts, CD26−/− mice showed an obviously enhanced tissue response and denser pulmonary infiltrates containing eosinophils around vessels and in the parenchyma after OVA sensitization and challenge. Serum IgG, including subclasses IgG1 and IgG2a, was greatly reduced in CD26−/− mice, but serum IgE remained unchanged. CD26−/− mice had increased mRNA expression of the Th2 cytokines IL‐4, IL‐5, and IL‐13 in the lungs compared with WT mice, whereas the levels of the pro‐Th1 cytokine IL‐12p40 were similar in both strains. Consequently, enhanced protein secretion of IL‐4, IL‐5, and IL‐13 was detected in bronchoa... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514907 Mon, 21 Nov 2011 05:00:00 +0100 5514907 http://www.medworm.com/index.php?rid=5514905&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141758 AbstractIn the thymus, developing T cells receive signals that determine lineage choice, specificity, MHC restriction and tolerance to self‐antigen. One way in which thymocytes receive instruction is by secretion of Sonic hedgehog (Shh) from thymic epithelial cells. We have previously shown that Hedgehog (Hh) signalling in the thymus decreases the CD4:CD8 single‐positive (SP) thymocyte ratio. Here, we present data indicating that double‐positive (DP) thymocytes are Hh‐responsive and that thymocyte‐intrinsic Hh signalling plays a role in modulating the production of CD4+ (SP4), CD8+ (SP8) and unconventional T‐cell subsets. Repression of physiological Hh signalling in thymocytes altered the proportions of DP and SP4 cells. Thymocyte‐intrinsic Hh‐dependent transcription also a... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5514905 Mon, 21 Nov 2011 05:00:00 +0100 5514905 http://www.medworm.com/index.php?rid=5431068&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141569 AbstractThe generation of effective type 1 T helper (Th1) cell responses is required for immunity against intracellular bacteria. However, some intracellular bacteria require interleukin (IL)‐17 to drive Th1‐cell immunity and subsequent protective host immunity. Here, in a model of Mycobacterium bovis Bacille Calmette Guerin (BCG) vaccination in mice, we demonstrate that the dependence on IL‐17 to drive Th1‐cell responses is a host mechanism to overcome bacteria‐induced IL‐10 inhibitory effects. We show that BCG‐induced prostaglandin‐E2 (PGE2) promotes the production of IL‐10 which limits Th1‐cell responses, while simultaneously inducing IL‐23 and Th17‐cell differentiation. The ability of IL‐17 to down‐regulate IL‐10 and induce IL‐12 production allows the ge... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431068 Mon, 21 Nov 2011 05:00:00 +0100 5431068 http://www.medworm.com/index.php?rid=5431067&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141987 AbstractThe proto‐oncogenes Myc and Pim1, which are deregulated in many types of cancers, are known to cooperate in B lymphoma development. Here we show that overexpression of retrovirally transduced, doxycycline‐inducible Myc alone in IL‐7‐deprived, growth‐arrested pre‐B cells enhanced cell cycle entry without impairing apoptosis. Overexpression of Pim1 decreased apoptosis, but had no effect on cell cycle entry. Co‐expression of Pim1 and Myc inhibited apoptosis and led to IL‐7‐independent proliferation of the transduced pre‐B cells in vitro, while blocking their differentiation to IgM+ immature cells. Transplantation of Pim1/Myc overexpressing pre‐BI cells into B‐cell deficient mice expanded the pre‐B‐cell compartments up to 100 fold within 4‐8 weeks. Transfo... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431067 Mon, 21 Nov 2011 05:00:00 +0100 5431067 http://www.medworm.com/index.php?rid=5431066&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141758 AbstractIn the thymus, developing T cells receive signals that determine lineage choice, specificity, MHC restriction and tolerance to self‐antigen. One way in which thymocytes receive instruction is by secretion of Sonic hedgehog (Shh) from thymic epithelial cells. We have previously shown that Hedgehog (Hh) signalling in the thymus decreases the CD4:CD8 single positive (SP) thymocyte ratio. Here we present data indicating that double positive (DP) thymocytes are Hh‐responsive and that thymocyte‐intrinsic Hh signalling plays a role in modulating the production of CD4+ (SP4), CD8+ (SP8) and unconventional T‐cell subsets. Repression of physiological Hh signalling in thymocytes altered the proportions of DP and SP4 cells. Thymocyte‐intrinsic Hh‐dependent transcription also attenu... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431066 Mon, 21 Nov 2011 05:00:00 +0100 5431066 http://www.medworm.com/index.php?rid=5431065&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201041295 AbstractThe differentiation and activation of T cells are critically modulated by MAP kinases, which are in turn feed‐back regulated by dual‐specificity phosphatases (DUSPs) to determine the duration and magnitude of MAP kinase activation. DUSP4 (also known as MKP2) is a MAP kinase‐induced DUSP member that is dynamically expressed during thymocyte differentiation. We generated DUSP4‐deficient mice to study the function of DUSP4 in T‐cell development and activation. Our results show that thymocyte differentiation and activation‐induced MAP kinase phosphorylation were comparable between DUSP4‐deficient and wild type mice. Interestingly, activated DUSP4‐/‐ CD4+ T cells were hyperproliferative while DUSP4‐/‐ CD8+ T cells proliferated normally. Further mechanistic studies ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431065 Mon, 21 Nov 2011 05:00:00 +0100 5431065 http://www.medworm.com/index.php?rid=5431064&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141871 AbstractTumour necrosis factor alpha (TNF‐α) is a major inducer for inflammation and bone loss. Here we investigated whether interleukin (IL)‐17 plays a role in TNF‐á mediated inflammation and bone resorption. Human TNFα transgenic (hTNFtg) mice were treated by neutralizing anti‐IL‐17A antibody and assessed for inflammation, cartilage and bone damage. T‐cell transcription factors and lymphokine patterns were measured in the lymph nodes. IL‐17A inhibition in the absence of IL‐1 was also evaluated by treating hTNFtg/IL‐1‐/‐ mice with IL‐17A neutralizing antibody. IL‐17A neutralization had only minor effects on TNF‐α induced inflammation but effectively reduced local and systemic bone loss by blocking osteoclast differentiation in vivo. Effects were based on a ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431064 Mon, 21 Nov 2011 05:00:00 +0100 5431064 http://www.medworm.com/index.php?rid=5431063&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141548 AbstractAs a hallmark of tuberculosis (TB), Mycobacterium tuberculosis (MTB) induces granulomatous lung lesions and systemic inflammatory responses during active disease. Molecular regulation of inflammation is associated with inflammasome assembly. We determined the extent to which MTB triggers inflammasome activation and how this impacts on the severity of TB in a mouse model. MTB stimulated release of mature IL‐1â in macrophages whilst attenuated M. bovis BCG failed to do so. Tubercle bacilli specifically activated the NLRP3 inflammasome and this propensity was strictly controlled by the virulence‐associated RD1 locus of MTB. However, Nlrp‐3‐deficient mice controlled pulmonary TB, a feature correlated with NLRP3‐independent production of IL‐1â in infected lungs. Our studie... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431063 Mon, 21 Nov 2011 05:00:00 +0100 5431063 http://www.medworm.com/index.php?rid=5431062&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201041038 In this study, we investigated the potential role of CD26 in ovalbumin (OVA)‐induced airway inflammation using CD26 gene knockout mice. Compared with wild type counterparts, CD26‐/‐ mice showed an obviously enhanced tissue response and denser pulmonary infiltrates containing eosinophils around vessels and in the parenchyma after OVA sensitisation and challenge. Serum IgG, including subclasses IgG1 and IgG2a, was greatly reduced in CD26‐/‐ mice, but serum IgE remained unchanged. CD26‐/‐ mice had increased mRNA expression of the Th2 cytokines IL‐4, IL‐5 and IL‐13 in the lungs compared with wild type mice, while levels of the pro‐Th1 cytokine IL‐12p40 was similar in both strains. Consequently, enhanced protein secretion of IL‐4, IL‐5 and IL‐13 was detected in bro... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431062 Mon, 21 Nov 2011 05:00:00 +0100 5431062 http://www.medworm.com/index.php?rid=5431061&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142091 AbstractTwo subsets of CD8+ T cells are generated early during an immune response; one of these subsets forms the memory pool, known as memory precursor effector cells (MPECs), identified by high expression of CD127 and low expression of KLRG1, whereas the other subset forms short lived effector cells (SLECs) identified by low expression of CD127 and high expression of KLRG1. Here we studied in vivo the role of type‐I IFN in this fate decision. We found that under priming conditions dominated by type‐I IFN, as observed in LCMV infection, type‐I IFN signaling directly impacted the regulation of T‐bet and thus the early fate decision of CD8+ T cells. In the absence of type‐I IFN signaling, CD8+ T cells failed to form SLECs but could form MPECs that give rise to functional memory CD... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5431061 Mon, 21 Nov 2011 05:00:00 +0100 5431061 http://www.medworm.com/index.php?rid=5423311&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22095445%26dopt%3DAbstract In this study, we examined several focal adhesion proteins during an inflammatory response. We found that there was selective loss of paxillin and focal adhesion kinase (FAK) from focal adhesions in proximity to transmigrating neutrophils; in contrast the levels of the focal adhesion proteins 1-integrin and vinculin were unaffected.Paxillin was lost from focal adhesions during neutrophil transmigration both under static and flow conditions.Down-regulating endothelial paxillin with siRNA blocked neutrophil transmigration while having no effect on rolling or adhesion.As paxillin dynamics are regulated partly by FAK, the role of FAK in neutrophil transmigration was examined using two complementary methods.siRNA was used to down-regulate total FAK protein while dominant-negative, kinase-defici... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423311 Thu, 17 Nov 2011 05:00:00 +0100 5423311 http://www.medworm.com/index.php?rid=5423313&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22076801%26dopt%3DAbstract Authors: Duchez S, Pascal V, Cogné N, Jayat-Vignoles C, Julien R, Cogné M Abstract B-cell fate and responses are modulated by soluble mediators and direct cellular interactions. Migration properties also vary during differentiation, commitment and activation. In many cells, modulation of responses to stimuli involves cell surface glycans, whose architecture depends on the simultaneous expression of multiple enzymes. By looking at the glycosylation-related gene expression patterns among B-cell populations, we determined in this study that the strongest variations were observed for CSGalNAcT-1 and EXTL1. These are enzymes involved in the biosynthesis of alternative forms of glycosaminoglycans (GAGs), namely chondroitin sulfate and heparan sulfate, respectively. These two enzymes sh... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423313 Thu, 10 Nov 2011 05:00:00 +0100 5423313 http://www.medworm.com/index.php?rid=5423312&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22076814%26dopt%3DAbstract Authors: Ansari AW, Heiken H, Meyer-Olson D, Schmidt RE Abstract Chemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role of chemokines and their receptors in viral infections including HIV-1 was predicted from the early studies of HIV-1 co-receptor CCR5 and its ligands and a divergent role of C-C chemokines in HIV-1 pathogenesis has been established. For example, CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES) have been shown to possess antiviral effects by binding to the HIV-1 co-receptor CCR5, whereas CCL2, a pro-inflammatory chemokine, supports HIV-1 replication despite being a member of same chemokine family. Furthermore, the well-esta... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423312 Thu, 10 Nov 2011 05:00:00 +0100 5423312 http://www.medworm.com/index.php?rid=5399832&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141676 AbstractChemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role of chemokines and their receptors in viral infections including HIV‐1 was predicted from the early studies of HIV‐1 co‐receptor CCR5 and its ligands and a divergent role of C‐C chemokines in HIV‐1 pathogenesis has been established. For example, CCL3 (MIP‐1α), CCL4 (MIP‐1β) and CCL5 (RANTES) have been shown to possess antiviral effects by binding to the HIV‐1 co‐receptor CCR5, whereas CCL2, a pro‐inflammatory chemokine, supports HIV‐1 replication despite being a member of same chemokine family. Furthermore, the well‐established role of CCL2 in driving the Th2 i... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5399832 Thu, 10 Nov 2011 05:00:00 +0100 5399832 http://www.medworm.com/index.php?rid=5399831&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201140865 AbstractB‐cell fate and responses are modulated by soluble mediators and direct cellular interactions. Migration properties also vary during differentiation, commitment and activation. In many cells, modulation of responses to stimuli involves cell surface glycans, whose architecture depends on the simultaneous expression of multiple enzymes. By looking at the glycosylation‐related gene expression patterns among B‐cell populations, we determined in this study that the strongest variations were observed for CSGalNAcT‐1 and EXTL1. These are enzymes involved in the biosynthesis of alternative forms of glycosaminoglycans (GAGs), namely chondroitin sulfate and heparan sulfate, respectively. These two enzymes showed inverse fluctuations in progenitors, resting B cells and activated B cel... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5399831 Thu, 10 Nov 2011 05:00:00 +0100 5399831 http://www.medworm.com/index.php?rid=5504127&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141924 AbstractThe activation of TLRs expressed by macrophages or DCs, in the long run, leads to persistently impaired functionality. TLR signals activate a wide range of negative feedback mechanisms; it is not known, however, which of these can lead to long‐lasting tolerance for further stimulatory signals. In addition, it is not yet understood how the functionality of monocyte‐derived DCs (MoDCs) is influenced in inflamed tissues by the continuous presence of stimulatory signals during their differentiation. Here we studied the role of a wide range of DC‐inhibitory mechanisms in a simple and robust model of MoDC inactivation induced by early TLR signals during differentiation. We show that the activation‐induced suppressor of cytokine signaling 1 (SOCS1), IL‐10, STAT3, miR146a and CD1... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5504127 Mon, 07 Nov 2011 05:00:00 +0100 5504127 http://www.medworm.com/index.php?rid=5504126&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141940 AbstractLyn, an Src‐family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn‐deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus‐like autoimmunity. We used flow cytometric analysis, BrdU labeling and our mathematical models of B‐cell population dynamics, to analyze how Lyn deficiency impacts B‐cell maturation and survival. We found that Lyn‐deficient transitional 1 (T1) cells develop normally, but T2 cells develop primarily from the T1 subset in the spleen and fail to also develop directly from BM immature B cells. Lyn‐deficient T2 cells either mature to the follicular B‐cell type at a close to normal rate, or die... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5504126 Mon, 07 Nov 2011 05:00:00 +0100 5504126 http://www.medworm.com/index.php?rid=5468220&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201142064 AbstractAmong synthetic vaccines, virus‐like particles (VLPs) are used for their ability to induce strong humoral responses. Very little is reported on VLP‐based‐vaccine‐induced CD4+ T‐cell responses, despite the requirement of helper T cells for antibody isotype switching. Further knowledge on helper T cells is also needed for optimization of CD8+ T‐cell vaccination. Here, we analysed human CD4+ T‐cell responses to vaccination with MelQbG10, which is a Qβ‐VLP covalently linked to a long peptide derived from the melanoma self‐antigen Melan‐A. In all analysed patients, we found strong antibody responses of mainly IgG1 and IgG3 isotypes, and concomitant Th1‐biased CD4+ T‐cell responses specific for Qβ. Although less strong, comparable B‐ and CD4+ T‐cell response... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5468220 Mon, 07 Nov 2011 05:00:00 +0100 5468220 http://www.medworm.com/index.php?rid=5423318&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22057556%26dopt%3DAbstract Authors: Van Roey GA, Arias MA, Tregoning JS, Rowe G, Shattock RJ Abstract The development of a successful vaccine against HIV is likely to require the induction of strong and long-lasting humoral immune responses at the mucosal portal of virus entry. Hence, the design of a vaccine strategy able to induce mucosal antibodies and in particular specific IgA, may be crucial to providing immune protection. Nasal immunisation is known to induce specific IgG and IgA responses in the cervicovaginal mucosa, however there is an urgent need for the development of safe, effective and accessible mucosal adjuvants for nasal application in humans. To reduce the potential for adverse events associated with some nasal adjuvants we have assessed whether the B-cell activating cytokines APRIL, BAFF an... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423318 Mon, 07 Nov 2011 05:00:00 +0100 5423318 http://www.medworm.com/index.php?rid=5423317&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22057588%26dopt%3DAbstract Authors: Fekete T, Szabo A, Beltrame L, Vivar N, Pivarcsi A, Lanyi A, Cavalieri D, Rajnavölgyi E, Rethi B Abstract The activation of Toll Like Receptors (TLRs) expressed by macrophages or dendritic cells (DCs), in the long run, leads to persistently impaired functionality. TLR signals activate a wide range of negative feedback mechanisms; it is not known however which of these can lead to long lasting tolerance for further stimulatory signals. In addition, it is not yet understood how the functionality of monocyte derived DCs (MoDCs) is influenced in inflamed tissues by the continuous presence of stimulatory signals during their differentiation. PMID: 22057588 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423317 Mon, 07 Nov 2011 05:00:00 +0100 5423317 http://www.medworm.com/index.php?rid=5423316&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22057631%26dopt%3DAbstract Authors: Shahaf G, Gross AJ, Sternberg-Simon M, Kaplan D, Defranco AL, Mehr R Abstract Lyn, a Src-family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn-deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus-like autoimmunity. We used flow cytometric analysis, BrdU labeling, and our mathematical models of B cell population dynamics, to analyze how Lyn deficiency impacts B-cell maturation and survival. We found that Lyn-deficient transitional 1 (T1) cells develop normally, but T2 cells develop primarily from the T1 subset in the spleen and fail to also develop directly from bone marrow immature B cells. Lyn-deficient T2 cel... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423316 Mon, 07 Nov 2011 05:00:00 +0100 5423316 http://www.medworm.com/index.php?rid=5423315&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22057654%26dopt%3DAbstract Authors: Chu VT, Berek C Abstract Eosinophils have multiple functions as effector cells of the innate immune system but also as modulators of immune responses. As producers of cytokines required for plasma cell survival, they are essential for the long-term maintenance of plasma cells in the bone marrow (BM). Here we show that activation of eosinophils both in vitro and in vivo enhances expression of the plasma cell survival factors APRIL, IL-6, IL-4, IL-10 and TNF-α. The in vivo activation of eosinophils is independent of the type of adjuvant used for primary immunization. Although eosinophils are activated by adjuvant itself, a stable activation and a constant increase in BM eosinophils is observed only in the presence of antigen. Thus, the numbers and the quality of eosinophils... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423315 Mon, 07 Nov 2011 05:00:00 +0100 5423315 http://www.medworm.com/index.php?rid=5423314&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22057679%26dopt%3DAbstract Authors: Braun M, Jandus C, Maurer P, Hammann-Haenni A, Schwarz K, Bachmann MF, Speiser DE, Romero P Abstract Among synthetic vaccines, virus-like particles (VLPs) are used for their ability to induce strong humoral responses. Very little is reported on VLP-based-vaccine-induced CD4(+) T-cell responses, despite the requirement of helper T cells for antibody isotype-switching. Further knowledge on helper T cells is also needed for optimization of CD8(+) T-cell vaccination. Here we analyzed human CD4(+) T-cell responses to vaccination with MelQbG10, which is a Qâ-VLP covalently linked to a long peptide derived from the melanoma self-antigen Melan-A. In all analyzed patients, we found strong antibody responses of mainly IgG1 and IgG3 isotypes, and concomitant Th1 biased CD4(+) T-cell... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5423314 Mon, 07 Nov 2011 05:00:00 +0100 5423314 http://www.medworm.com/index.php?rid=5399828&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141787 AbstractThe development of a successful vaccine against HIV is likely to require the induction of strong and long‐lasting humoral immune responses at the mucosal portal of virus entry. Hence, the design of a vaccine strategy able to induce mucosal antibodies and in particular specific IgA, may be crucial to providing immune protection. Nasal immunisation is known to induce specific IgG and IgA responses in the cervicovaginal mucosa, however there is an urgent need for the development of safe, effective and accessible mucosal adjuvants for nasal application in humans. To reduce the potential for adverse events associated with some nasal adjuvants we have assessed whether the B‐cell activating cytokines APRIL, BAFF and TSLP enhance humoral immune responses to HIV‐1 gp140. Following int... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5399828 Mon, 07 Nov 2011 05:00:00 +0100 5399828 http://www.medworm.com/index.php?rid=5399827&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141924 AbstractThe activation of Toll Like Receptors (TLRs) expressed by macrophages or dendritic cells (DCs), in the long run, leads to persistently impaired functionality. TLR signals activate a wide range of negative feedback mechanisms; it is not known however which of these can lead to long lasting tolerance for further stimulatory signals. In addition, it is not yet understood how the functionality of monocyte derived DCs (MoDCs) is influenced in inflamed tissues by the continuous presence of stimulatory signals during their differentiation. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5399827 Mon, 07 Nov 2011 05:00:00 +0100 5399827 http://www.medworm.com/index.php?rid=5399826&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141940 AbstractLyn, a Src‐family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn‐deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus‐like autoimmunity. We used flow cytometric analysis, BrdU labeling, and our mathematical models of B cell population dynamics, to analyze how Lyn deficiency impacts B‐cell maturation and survival. We found that Lyn‐deficient transitional 1 (T1) cells develop normally, but T2 cells develop primarily from the T1 subset in the spleen and fail to also develop directly from bone marrow immature B cells. Lyn‐deficient T2 cells either mature to the follicular B‐cell type at a close to normal rate,... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5399826 Mon, 07 Nov 2011 05:00:00 +0100 5399826 http://www.medworm.com/index.php?rid=5399825&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141953 AbstractEosinophils have multiple functions as effector cells of the innate immune system but also as modulators of immune responses. As producers of cytokines required for plasma cell survival, they are essential for the long‐term maintenance of plasma cells in the bone marrow (BM). Here we show that activation of eosinophils both in vitro and in vivo enhances expression of the plasma cell survival factors APRIL, IL‐6, IL‐4, IL‐10 and TNF‐α. The in vivo activation of eosinophils is independent of the type of adjuvant used for primary immunization. Although eosinophils are activated by adjuvant itself, a stable activation and a constant increase in BM eosinophils is observed only in the presence of antigen. Thus, the numbers and the quality of eosinophils are dependent on primin... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5399825 Mon, 07 Nov 2011 05:00:00 +0100 5399825 http://www.medworm.com/index.php?rid=5449423&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141950 AbstractThe TNF receptor superfamily member death receptor 3 (DR3) exacerbates Th2 and Th17‐mediated inflammatory and autoimmune conditions, yet no role in host defence has been reported. Here we examined the role of DR3 during infection with Salmonella enterica serovar Typhimurium. Infection resulted in protracted expression of the DR3 ligand TL1A but not the related TNF superfamily proteins OX40L or CD30L. TL1A expression was localized to splenic F4/80+ macrophages where S. enterica Typhimurium replicates, and temporally coincided with the onset of CD4+‐cell expansion. To address the relevance of the TL1A‐DR3 interaction, we examined immune responses to S. enterica Typhimurium in mice lacking DR3. Infected DR3‐/‐ mice harboured reduced numbers of antigen‐experienced and proli... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5449423 Tue, 01 Nov 2011 04:00:00 +0100 5449423 http://www.medworm.com/index.php?rid=5440077&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.201141832 AbstractPost‐transplantation lymphoproliferative disorders (PTLD) are life‐threatening complications of organ transplantation caused by EBV infection and the use of chronic immunosuppression. While T cell impairment is known to play a critical role in the immunopathogenesis of EBV complications post‐transplantation, the role of NK cells is still under investigation. Here we have characterized NK cell phenotype and function in peripheral blood from asymptomatic pediatric thoracic transplant patients, patients with PTLD, and healthy controls. Overall, asymptomatic pediatric Tx patients presented significant expansion of the CD56brightCD16± subset and displayed effective NK cell function, while PTLD patients accumulated CD56dimCD16‐ and CD56‐CD16+ NK cell subsets. In addition, NK c... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=5440077 Tue, 01 Nov 2011 04:00:00 +0100 5440077