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European Journal of Immunology

Sarah A Overall, Dorothée Bourges, Ian R van Driel, Paul A Gleeson
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H(+) /K(+) ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice...
October 19, 2016: European Journal of Immunology
Guoping Fu, Mei Yu, Yuhong Chen, Yongwei Zheng, Wen Zhu, Debra K Newman, Demin Wang, Renren Wen
Pre-T cell receptor (TCR) signaling is required for pre-T cell survival, proliferation, and differentiation from the CD4 and CD8 double negative (DN) to the double positive (DP) stage. However, the pre-TCR signal transduction pathway is not fully understood and the signaling molecules involved have not been completely identified. Phospholipase Cγ (PLCγ) 1 is an important signaling molecule that generates two second messengers, diacylglycerol and inositol 1,4,5-trisphosphate, that are important to mediate PKC activation and intracellular Ca(2+) flux in many signaling pathways...
October 19, 2016: European Journal of Immunology
Jennifer L Gardell, David C Parker
The delivery of T-cell help to B cells is antigen-specific, MHC-restricted, and CD40L (CD154) dependent. It has been thought that when a T cell recognizes an antigen-presenting B cell, CD40L expressed on the T-cell surface engages with CD40 on the surface of B cells as long as the cells remain conjugated. To study this, we added fluorescently labeled anti-CD40L antibody during overnight incubation of antigen-presenting B cells with antigen-specific T cells. We discovered that CD40L does not remain on the surface of the T cell, but it is transferred to and endocytosed by B cells receiving T-cell help...
October 18, 2016: European Journal of Immunology
Jan Klocke, Katharina Kopetschke, Anna-Sophie Grießbach, Valerie Langhans, Jens Y Humrich, Robert Biesen, Duska Dragun, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten, Philipp Enghard
Renal infiltration of inflammatory cells contributes to the pathogenesis of Lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokines were significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity...
October 18, 2016: European Journal of Immunology
Yohei Manabe, Marie Yoshimura, Kazuma Sakamaki, Asuka Inoue, Aya Kakinoki, Satoshi Hokari, Mariko Sakanaka, Junken Aoki, Hiroyuki Miyachi, Kazuyuki Furuta, Satoshi Tanaka
Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow-derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1-chloro-2,4-dinitrobenzene and 1-fluoro-2,4-dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells...
October 17, 2016: European Journal of Immunology
Yohei Kawano, Georg Petkau, Ingrid Wolf, Julia Tornack, Fritz Melchers
Long-term proliferating, DH JH -rearranged mouse precursor B-cell lines have previously been established in serum- and IL-7-containing media from fetal liver, but not from bone marrow. Serum and stromal cells expose these pre-B cells to undefined factors, hampering accurate analyses of ligand-dependent signalling, which controls pre-B cell proliferation, survival, residence and migration. Here, we describe a novel serum-free, stromal cell-free culture system, which allows to establish and maintain pre-B cells not only from fetal liver, but also from bone marrow with practically identical efficiencies in proliferation, cloning and differentiation...
October 14, 2016: European Journal of Immunology
Achire N Mbanwi, Chao Wang, Kaoru Geddes, Dana J Philpott, Tania H Watts
Lymphocytic choriomeningitis virus clone 13 (LCMV13) infection of mice is a widely used model for investigating the mechanisms driving persistent viral infection in humans. LCMV13 disrupts splenic architecture early during infection, but this returns to normal within a few weeks. However, the long-term effects of LCMV13 infection on splenic structure have not been reported. Here we report that persistent infection with LCMV13 results in sustained splenic atrophy that persists for at least 500 days following infection, whereas infection with the acutely infecting LCMV Armstrong is associated with a return to pre-infection spleen weights...
October 11, 2016: European Journal of Immunology
Béatrice Breart, Philippe Bousso
T cells are sequestered for several days in lymph nodes following antigen recognition but the precise mechanism regulating their timing of egress is not fully understood. In particular, whether interactions with antigen-presenting cells (APCs) and/or strength of the TCR stimulation shape T-cell residence time is unclear. We report here that the probability of T-cell egress decreases upon stimulation with high affinity TCR ligands. In contrast, low affinity peptides favor early egress, a phenomenon that could be reversed by sustaining antigen availability...
October 11, 2016: European Journal of Immunology
Alexander Puck, Stefan Hopf, Madhura Modak, Otto Majdic, Petra Cejka, Stephan Blüml, Klaus Schmetterer, Catharina Arnold-Schrauf, Jens G Gerwien, Klaus S Frederiksen, Elisabeth Thell, Judith Leitner, Peter Steinberger, Regina Aigner, Maria Seyerl-Jiresch, Gerhard J Zlabinger, Johannes Stöckl
The cytoplasmic tail of CD45 (ct-CD45) is proteolytically cleaved and released upon activation of human phagocytes. It acts on T cells as an inhibitory, cytokine-like factor in vitro. Here we show, that ct-CD45 is abundant in human peripheral blood plasma from healthy adults compared with plasma derived from umbilical cord blood and plasma from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Plasma depleted of ct-CD45 enhanced T-cell proliferation, while addition of exogenous ct-CD45 protein inhibited proliferation and reduced cytokine production of human T lymphocytes in response to TCR signaling...
October 8, 2016: European Journal of Immunology
Andreas Brandl, Patrick Daum, Sven Brenner, Sebastian R Schulz, Desmond Yat-Hin Yap, Michael R Bösl, Jürgen Wittmann, Wolfgang Schuh, Hans-Martin Jäck
microRNAs (miRNAs) are important posttranscriptional regulators during hematopoietic lineage commitment and lymphocyte development. Mature miRNAs are processed from primary miRNA transcripts in two steps by the microprocessor complex, consisting of Drosha and its partner DiGeorge Critical Region 8 (DGCR8), and the RNAse III enzyme, Dicer. Conditional ablations of Drosha and Dicer have established the importance of both RNAses in B- and T-cell development. Here, we show that a cre-mediated B-cell specific deletion of DGCR8 in mice results in a nearly complete maturation block at the transition from the pro-B to the pre-B cell stage, and a failure to upregulate Ig μ heavy chain expression in pro-B cells...
October 5, 2016: European Journal of Immunology
Jorg van Loosdregt, Maura Rossetti, Roberto Spreafico, Maryam Moshref, Merissa Olmer, Gary W Williams, Pavanish Kumar, Dana Copeland, Ken Pischel, Martin Lotz, Salvatore Albani
Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4(+) T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of CD4(+) T cells in the autoimmune process. A better knowledge of the mechanisms determining such impaired homeostasis could contribute significantly to both the understanding and the treatment of the disease. Here we investigated whether autophagy, is dysregulated in CD4(+) T cells of RA patients, resulting in disturbed T-cell homeostasis...
October 5, 2016: European Journal of Immunology
Sebastian Fuchs, Petra Kaiser-Labusch, Julia Bank, Sandra Ammann, Anja Kolb-Kokocinski, Christine Edelbusch, Heymut Omran, Stephan Ehl
Tyrosine kinase 2 (TYK2) associates with interferon (IFN) alpha receptor, IL-10 receptor (IL-10R) beta and other cytokine receptor subunits for signal transduction, in response to various cytokines, including type-I and type-III IFNs, IL-6, IL-10, IL-12 and IL-23. Data on TYK2 dependence on cytokine responses and in vivo consequences of TYK2 deficiency are inconsistent. We investigated a TYK2 deficient patient, presenting with eczema, skin abscesses, respiratory infections and IgE levels >1000 U/mL, without viral or mycobacterial infections and a corresponding cellular model to analyze the role of TYK2 in type-III IFN mediated responses and NK-cell function...
October 5, 2016: European Journal of Immunology
Li Jiang, Shuyu Yao, Su Huang, Jeffrey Wright, Thomas J Braciale, Jie Sun
Recent evidence has suggested that IL-10-producing effector CD8(+) T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8(+) T cells are not completely defined. Here we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8(+) T cells during influenza virus infection in mice. We find that type I IFNs can enhance IL-27 production by lung antigen presenting cells, thereby facilitating IL-10-producing CD8(+) T-cell development through a CD8(+) T cell non-autonomous way...
October 4, 2016: European Journal of Immunology
Natasha Dubois Cauwelaert, Susan L Baldwin, Mark T Orr, Anthony L Desbien, Emily Gage, Kimberly A Hofmeyer, Rhea N Coler
The contribution of B cells to immunity against many infectious diseases is unquestionably important and well characterized. Here, we sought to determine the role of B cells in the induction of T helper 1 (TH 1) CD4(+) T cells upon vaccination with a tuberculosis (TB) antigen combined with a TLR4 agonist. We used B-cell deficient mice (μMT(-/-) ), tetramer-positive CD4(+) T cells, markers of memory 'precursor' effector cells (MPECs), and T-cell adoptive transfers and demonstrated that the early antigen-specific cytokine-producing TH 1 responses are unaffected in the absence of B cells, however MPEC induction is strongly impaired resulting in a deficiency of the memory TH 1 response in μMT(-/-) mice...
October 4, 2016: European Journal of Immunology
Nasr Y A Hemdan, Cynthia Weigel, Christina-Maria Reimann, Markus H Gräler
Sepsis is a systemic inflammatory response to pathogens and a leading cause of hospital related mortality worldwide. Sphingosine 1-phosphate (S1P) regulates multiple cellular processes potentially involved in the pathogenesis of sepsis, including antigen presentation, lymphocyte egress, and maintenance of vascular integrity. We thus explored the impact of manipulating S1P signaling in experimental polymicrobial sepsis in mice. Administration of 4-deoxypyridoxine (DOP), an inhibitor of the S1P-degrading enzyme S1P-lyase, or of the sphingosine analogue FTY720 that serves as an S1P receptor agonist after phosphorylation ameliorated morbidity, improved recovery from sepsis in surviving mice, and reduced sepsis-elicited hypothermia and body weight loss...
September 29, 2016: European Journal of Immunology
Eliseo F Castillo, Handong Zheng, Christian Van Cabanlong, Fei Dong, Yan Luo, Yi Yang, Meilian Liu, Winston W-Y Kao, Xuexian O Yang
TH17 cells play an essential role in the development of both human multiple sclerosis and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, it is not well understood how the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation. In vitro, we found Lumican (Lum), an extracellular matrix protein, is selectively expressed by TH17 cells among tested murine TH subsets. Lum-deficiency leads to earlier onset and enhanced severity of experimental autoimmune encephalomyelitis...
September 29, 2016: European Journal of Immunology
Robrecht Cannoodt, Wouter Saelens, Saey Yvan
Recent developments in single-cell transcriptomics have opened new opportunities for studying dynamic processes in immunology in a high-throughput and unbiased manner. Starting from a mixture of cells in different stages of a developmental process, unsupervised trajectory inference algorithms aim to automatically reconstruct the underlying developmental path that cells are following. In this review, we break down the strategies used by this novel class of methods, and organize their components into a common framework, highlighting several practical advantages and disadvantages of the individual methods...
September 28, 2016: European Journal of Immunology
Ine Jorgensen, Joseph P Lopez, Stefan A Laufer, Edward A Miao
Inflammasomes activate caspase-1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore-induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT, with its associated bacteria, by neutrophils; bacteria are subsequently killed via neutrophil ROS...
September 28, 2016: European Journal of Immunology
Toshimitsu Kajiwara, Tsutomu Tanaka, Kazuharu Kukita, Goro Kutomi, Keita Saito, Koichi Okuya, Akari Takaya, Vitaly Kochin, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe, Koichi Hirata, Noriyuki Sato, Yasuaki Tamura
To establish an effective cancer immunotherapy, it is crucial that cancer cells present a cancer-specific antigen in a hypoxic area, a hallmark of the tumor microenvironment. Here we show the impact of hypoxia on MHC class I antigen presentation in vitro and in vivo in murine tumors. Activation of antigen-specific CTLs by tumor cells that had been pre-incubated under a condition of hypoxia was enhanced compared with that by tumor cells pre-incubated under a condition of normoxia. Cell surface expression of MHC class I-peptide complex on the tumor cells was increased under a condition of hypoxia, thereby leading to higher susceptibility to specific CTLs...
September 26, 2016: European Journal of Immunology
Tamara H Ramwadhdoebe, Janine Hähnlein, Karen I Maijer, Leonard J van Boven, Danielle M Gerlag, Paul P Tak, Lisa G M van Baarsen
The balance between proinflammatory and regulatory CD4(+) T cells is tightly controlled in lymphoid organs. In autoimmune diseases this balance is altered in the periphery and target tissue of patients. However, not much is known about the balance initiated in lymphoid organs during the development of disease. Since systemic autoimmunity is present years before the clinical manifestations of rheumatoid arthritis (RA), it is possible to study the immunoregulatory balance during the earliest (preclinical) phases of disease...
September 20, 2016: European Journal of Immunology
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