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European Journal of Immunology

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https://www.readbyqxmd.com/read/29786142/the-bone-marrow-is-not-only-a-primary-lymphoid-organ-the-critical-role-for-t-lymphocyte-migration-and-housing-of-long-term-memory-plasma-cells
#1
REVIEW
Reinhard Pabst
In immunology and anatomy textbooks the bone marrow is described as a typical "primary lymphoid organ" producing lymphoid cells independent of antigens. The hematopoietic bone marrow is largely age-dependent organ with great anatomical and functional differences among various species. There are estimates that about 12 % of all lymphoid cells in the human body are found in the bone marrow at any given time (2 % in the peripheral blood). Enormous numbers of T lymphocytes migrate to the bone marrow and partly return later to the blood...
May 22, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29762870/t-cells-and-ilc2s-are-major-effector-cells-in-influenza-induced-exacerbation-of-allergic-airway-inflammation-in-mice
#2
Bobby W S Li, Marjolein J W de Bruijn, Melanie Lukkes, Menno van Nimwegen, Ingrid M Bergen, Alex KleinJan, Corine H GeurtsvanKessel, Arno Andeweg, Guus F Rimmelzwaan, Rudi W Hendriks
Influenza virus infection is an important cause of severe asthma exacerbations, but it remains unclear how a Th1-mediated antiviral response triggers a prototypical Th2 disease. We investigated CD4+ T cells and group 2 innate lymphoid cells (ILC2s) in influenza virus-infected mice. We found that ILC2s accumulated in the lung rapidly after influenza virus infection, but the induction of IL-5 and IL-13 secretion was delayed and concomitant with T cell activation. In an influenza-induced exacerbation of allergic airway inflammation model we noticed an initial reduction of ILC2 numbers and cytokine production in broncho-alveolar lavage compared to chronic house dust mite (HDM)-mediated airway inflammation alone...
May 15, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29749611/proteomic-definition-of-human-mucosal-associated-invariant-t-cells-determines-their-unique-molecular-effector-phenotype
#3
Björn Bulitta, Werner Zuschratter, Isabel Bernal, Dunja Bruder, Frank Klawonn, Martin von Bergen, Henrikus Stephanus Paulus Garritsen, Lothar Jänsch
Mucosal-associated invariant T cells (MAIT) constitute the most abundant anti-bacterial CD8+ T cell population in humans. MR1/TCR-activated MAIT cells were reported to organize cytotoxic and innate-like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non-MAIT CD8+ T cells (cCD8+ ) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8+ T cells and NK cells donor-independently...
May 11, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29745988/differential-requirements-for-irf4-in-the-clonal-expansion-and-homeostatic-proliferation-of-naive-and-memory-murine-cd8-t-cells
#4
Mana Miyakoda, Kiri Honma, Daisuke Kimura, Masoud Akbari, Kazumi Kimura, Toshifumi Matsuyama, Katsuyuki Yui
Interferon regulatory factor 4 (IRF4) has critical roles in immune cell differentiation and function and is indispensable for clonal expansion and effector function in T cells. Here, we demonstrate that the AKT pathway is impaired in murine CD8+ T cells lacking IRF4. The expression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT pathway, was elevated in Irf4-/- CD8+ T cells. Inhibition of PTEN partially rescued downstream events, suggesting that PTEN constitutes a checkpoint in the IRF4-mediated regulation of cell signaling...
May 10, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29738081/prame-peptide-specific-cd8-t-cells-represent-the-predominant-response-against-leukemia-associated-antigens-laas-in-healthy-individuals
#5
Sarah Matko, Julia Manderla, Maria Bonsack, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
Antigen-specific T cells isolated from healthy individuals (HIs) have shown great therapeutic potential upon adoptive transfer for the treatment of viremia in immunosuppressed patients. The lack of comprehensive data on the prevalence and characteristics of leukemia associated antigen (LAA)-specific T cells in HIs still limits such an approach for tumor therapy. Therefore, we have investigated T cell responses against prominent candidates comprising WT1, PRAME, Survivin, NY-ESO and p53 by screening PBMCs from HIs using intracellular IFN-γ staining following provocation with LAA peptide mixes...
May 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29733429/the-enigmatic-function-of-igd-some-answers-at-last
#6
REVIEW
Cindy Gutzeit, Kang Chen, Andrea Cerutti
IgD emerged soon after IgM at the time of inception of the adaptive immune system. Despite its evolutionary conservation from fish to humans, the specific functions of IgD have only recently begun to be elucidated. Mature B cells undergo alternative mRNA splicing to express IgD and IgM receptors with identical antigenic specificity. The enigma of dual IgD and IgM expression has been tackled by several recent studies showing that IgD helped peripheral accumulation of physiologically autoreactive B cells through its functional unresponsiveness to self-antigens but prompt readiness against foreign antigens...
May 7, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29729112/the-il-33-st2-myd88-axis-promotes-regulatory-t-cell-proliferation-in-the-murine-liver
#7
Lei Xu, Wei Li, Xiaofan Wang, Lina Zhang, Qianqian Qi, Liyang Dong, Chuan Wei, Yanan Pu, Yalin Li, Jifeng Zhu, Sha Zhou, Feng Liu, Xiaojun Chen, Chuan Su
Hepatic Foxp3+ Treg cells are crucial for maintaining local immune homeostasis in the liver. However, the environmental cues required for hepatic Treg cell homeostasis are unclear. In this study, we showed that the IL-33 receptor ST2 was preferentially expressed on Treg cells in the mouse liver, but it was more lowly expressed in the spleen, mesenteric lymph nodes, and blood. More importantly, we found that IL-33 promoted the proliferation of hepatic Treg cells through myeloid differentiation factor MyD88 signaling concomitant with increased cyclin-dependent kinase (CDK) 4 and cyclin D1 expression...
May 5, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29719048/serotonin-decreases-the-production-of-th1-th17-cytokines-and-elevates-the-frequency-of-regulatory-cd4-t-cell-subsets-in-multiple-sclerosis-patients
#8
Priscila M Sacramento, Clarice Monteiro, Aleida S O Dias, Taissa M Kasahara, Thaís B Ferreira, Joana Hygino, Ana Cristina Wing, Regis M Andrade, Fernanda Rueda, Marisa C Sales, Claudia Cristina Vasconcelos, Cleonice A M Bento
Excessive levels of pro-inflammatory cytokines in the central nervous system (CNS) are associated with reduced serotonin (5-HT) synthesis, a neurotransmitter with diverse immune effects. In this study, we evaluated the ability of exogenous 5-HT to modulate the T-cell behavior of patients with multiple sclerosis (MS), a demyelinating autoimmune disease mediated by Th1 and Th17 cytokines. Here, 5-HT attenuated, in vitro, T-cell proliferation and Th1 and Th17 cytokines production in cell cultures from MS patients...
May 2, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29710424/inhibitors-of-elastase-stimulate-murine-b-lymphocyte-differentiation-into-igg-and-iga-producing-cells
#9
Zayed Attia, John C Rowe, Eunsoo Kim, Sanjay Varikuti, Haley H Steiner, Ahmad Zaghawa, Hany Hassan, Estelle Cormet-Boyaka, Abhay R Satoskar, Prosper N Boyaka
It is well established that dendritic cells and macrophages play a role in antigen presentation to B and T cells and in shaping B and T cell responses via cytokines they produce. We have previously reported that depletion of neutrophils improves the production of mucosal IgA after sublingual immunization with Bacillus anthracis edema toxin as adjuvant. These past studies also demonstrated that an inverse correlation exists between the number of neutrophils and production of IgA by B cells. Using specific inhibitors of elastase, we addressed whether the elastase activity of neutrophil could be the factor that interferes with production of IgA and possibly other immunoglobulin isotypes...
April 30, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29697861/microglial-mhc-class-ii-is-dispensable-for-experimental-autoimmune-encephalomyelitis-and-cuprizone-induced-demyelination
#10
Yochai Wolf, Anat Shemer, Liron Levy-Efrati, Mor Gross, Jung-Seok Kim, Adrien Engel, Eyal David, Louise Chappell-Maor, Jonathan Grozovski, Ron Rotkopf, Inbal Biton, Raya Eilam-Altstadter, Steffen Jung
Microglia are resident immune cells in the central nervous system (CNS), strategically positioned to clear dead cells and debris, and orchestrate CNS inflammation and immune defense. In steady state, these macrophages lack major histocompatibility complex class II (MHCII) expression, but microglia activation can be associated with MHCII induction. Whether microglial MHCII serves antigen presentation for critical local T cell re-stimulation in CNS auto-immune disorders or modulates microglial signaling output remains under debate...
April 26, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29697856/induced-cns-expression-of-cxcl1-augments-neurologic-disease-in-a-murine-model-of-multiple-sclerosis-via-enhanced-neutrophil-recruitment
#11
Jonathan J Grist, Brett S Marro, Dominic D Skinner, Amber R Syage, Colleen Worne, Daniel J Doty, Robert S Fujinami, Thomas E Lane
Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE...
April 26, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29684247/tr1-cell-immunotherapy-promotes-transplant-tolerance-via-de-novo-tr1-cell-induction-in-mice-and-is-safe-and-effective-during-acute-viral-infection
#12
Tatiana Jofra, Roberta Di Fonte, Giuseppe Galvani, Mirela Kuka, Matteo Iannacone, Manuela Battaglia, Georgia Fousteri
Tr1 cell therapy is considered an emerging approach to improve transplant tolerance and enhance allogeneic graft survival. However, it remains unclear how Tr1 cells promote transplant tolerance and whether they will be safe and stable in the face of an acute viral infection. By employing a mouse model of pancreatic islet transplantation, we report that Tr1 cell therapy promoted transplant tolerance via de novo induction of Tr1 cells in the recipients. Acute viral infection with lymphocytic choriomeningitis virus (LCMV) had no impact on Tr1 cell number and function, neither on the Tr1 cells infused nor on the ones induced, and that was reflected in the robust maintenance of the graft...
April 23, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29677388/engulfment-of-hb-activated-platelets-differentiates-monocytes-into-pro-inflammatory-macrophages-in-pnh-patients
#13
Rashi Singhal, Sheetal Chawla, Harish Batra, Sameer Gupta, Amrita Ojha, Deepak K Rathore, Tulika Seth, Prasenjit Guchhait
The distinct response shown by different phenotypes of macrophages and monocytes under various clinical conditions have put the heterogeneity of these cells into focus of investigation for several diseases. Recently we have described that after engulfing Hb-activated platelets, classical monocytes differentiated into pro-inflammatory phenotypes, which were abundant in the circulation of PNH and SCD patients. Our current study shows that upon engulfment of Hb-activated platelets, monocytes differentiate into M1-macrophages under M1-polarization stimulus (GM-CSF, IFN-γ+LPS)...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29677387/il13r%C3%AE-2-expression-identifies-tissue-resident-il-22-producing-plzf-innate-t-cells-in-the-human-liver
#14
Dominic Paquin-Proulx, Benjamin C Greenspun, Lise Pasquet, Benedikt Strunz, Soo Aleman, Karolin Falconer, Masaki Terabe, Jay A Berzofsky, Johan K Sandberg, Espen Melum, Douglas F Nixon, Niklas K Björkström
Innate lymphocytes are selectively enriched in the liver where they have important roles in liver immunology. Murine studies have shown that type I NKT cells can promote liver inflammation whereas type II NKT cells have an anti-inflammatory role. In humans, type II NKT cells were found to accumulate in the gut during inflammation and IL13Rα2 was proposed as a marker for these cells. In the human liver, less is known about type I and II NKT cells. Here, we studied the phenotype and function of human liver T cells expressing IL13Rα2...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29676785/sustained-cross-presentation-capacity-of-murine-splenic-dendritic-cell-subsets-in-vivo
#15
Nataschja I Ho, Marcel G M Camps, Edwin F E de Haas, Ferry Ossendorp
An exclusive feature of dendritic cells (DCs) is their ability to cross-present exogenous antigens in MHC class I molecules. We analyzed the fate of protein antigen in antigen presenting cell (APC) subsets after uptake of naturally formed antigen-antibody complexes in vivo. We observed that murine splenic DC subsets were able to present antigen in vivo for at least a week. After ex vivo isolation of four APC subsets, the presence of antigen in the storage compartments was visualized by confocal microscopy. Although all APC subsets stored antigen for many days, their ability and kinetics in antigen presentation was remarkably different...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29676784/expression-and-characterisation-of-%C3%AE-v%C3%AE-5-integrin-on-intestinal-macrophages
#16
Ashok K Kumawat, Chen Yu, Elizabeth A Mann, Anika Schridde, Silvia C Finnemann, Allan McI Mowat
Macrophages play a crucial role in maintaining homeostasis in the intestine, but the underlying mechanisms have not yet been elucidated fully. Here we show for the first time that mature intestinal macrophages in mouse colon and small intestine express high levels of αvβ5 integrin, which acts as a receptor for the uptake of apoptotic cells and can activate molecules involved in several aspects of tissue homeostasis such as angiogenesis and remodelling of the extracellular matrix. αvβ5 is not expressed by other immune cells in the intestine, is already present on intestinal macrophages soon after birth, and its expression is not dependent on the microbiota...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29676458/an-optimized-method-to-measure-human-foxp3-regulatory-t-cells-from-multiple-tissue-types-using-mass-cytometry
#17
Nicholas A J Dawson, Avery J Lam, Laura Cook, Romy E Hoeppli, Raewyn Broady, Anne M Pesenacker, Megan K Leving
Mass cytometry has facilitated the discovery of complex immunological networks and immune cell interactions; however, there are limited reports of using this technology to measure expression of intranuclear antigens such as transcription factors. Herein we describe testing of multiple staining methods to detect FOXP3, the lineage-defining transcription factor for regulatory T cells (Tregs), by mass cytometry. A custom paraformaldehyde/saponin-based fixation and permeabilization method was found to be the optimal method for mass cytometry-based Treg detection, yielding the best balance of FOXP3 detection and preserved cell surface marker expression...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29671873/t-cell-derived-ifn-%C3%AE-downregulates-protective-group-2-innate-lymphoid-cells-in-murine-lupus-erythematosus
#18
Mathis Düster, Martina Becker, Ann-Christin Gnirck, Malte Wunderlich, Ulf Panzer, Jan-Eric Turner
Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3+ IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Faslpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE)...
April 19, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29645094/leishmania-amazonensis-downregulates-macrophage-inos-expression-via-histone-deacetylase-1-hdac1-a-novel-parasite-evasion-mechanism
#19
Teresa C Calegari-Silva, Áislan C Vivarini, Renata de M S Pereira, Karina L Dias-Teixeira, Carolina T Rath, Amanda S S Pacheco, Gabrielle B L Silva, Charlene A S Pinto, José V Dos Santos, Alessandra M Saliba, Carlos E P Corbett, Claudia M de Castro Gomes, Nicolas Fasel, Ulisses G Lopes
The induced expression of nitric oxide synthase (iNOS) controls the intracellular growth of Leishmania in infected macrophages. Histones deacetylases (HDACs) negatively regulate gene expression through the formation of complexes containing transcription factors such as NF-κB p50/50. Herein, we demonstrated the occupancy of p50/p50_HDAC1 to iNOS promoter associated with reduced levels of H3K9Ac. Remarkably, we found increased levels of HDAC1 in L. amazonensis-infected macrophages. HDAC1 upregulation was not found in L...
April 12, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29644627/routinely-used-immunoassays-do-not-detect-circulating-anti-gbm-antibodies-against-native-nc1-hexamer-and-ea-epitope-of-the-%C3%AE-3-chain-of-type-iv-collagen
#20
LETTER
Giovanna Clavarino, Arnaud Gauthier, Thomas Hellmark, Pierre-Louis Carron, Diane Giovannini, Sophie Colliard, Marie-Agnès Dragon-Durey, Mårten Segelmark, Jean-Yves Cesbron, Chantal Dumestre-Pérard
Goodpasture syndrome or anti-glomerular basement membrane (anti-GBM) disease, a rare autoimmune vasculitis, is a therapeutic emergency. Autoimmune exploration is crucial since an early diagnosis is essential for survival and renal function recovery. Currently, immunoassays using the non-collagen region (NC1) of the alpha3 subunit of collagen type IV (alpha3(IV)NC1) as antigen are the most frequently used for the detection of circulating anti-GBM antibodies. We report the presence of circulating anti-GBM antibodies directed against the native NC1 hexamer or the EA epitope of alpha3, that were not detected using routine immunoassays but that were positive by indirect immunofluorescence, highlighting the risk of false negative results of these assays with dramatic consequences for the patients in term of renal but also of life survival...
April 12, 2018: European Journal of Immunology
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