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European Journal of Immunology

Anita N Kremer, Marijke I Zonneveld, Andreas E Kremer, Edith D van der Meijden, J H Frederik Falkenburg, Marca H M Wauben, Esther N M Nolte-'t Hoen, Marieke Griffioen
CD4 T-cells play a central role as helper cells in adaptive immunity. Presentation of exogenous antigens in MHC class II by professional antigen-presenting cells is a crucial step in induction of specific CD4 T-cells in adaptive immune responses. For efficient induction of immunity against intracellular threats such as viruses or malignant transformations, antigens from HLA class II-negative infected or transformed cells need to be transferred to surrounding antigen-presenting cells to allow efficient priming of naive CD4 T-cells...
July 16, 2018: European Journal of Immunology
Jürgen Brück, Ivana Glocova, Julia Geisel, Christina Kellerer, Martin Röcken, Kamran Ghoreschi
Dimethyl fumarate (DMF) promotes an IL-17Alow IFN-γlow IL-4+ CD4+ T cell phenotype. Adoptive transfer of in vitro DMF-treated myelin peptide-reactive IL-17Alow IFN-γlow IL-4+ CD4+ T cells prior to immunization for EAE reduces the severity of encephalomyelitis. This beneficial effect of transferred DMF-treated CD4+ T cells requires an early in vivo recall. This article is protected by copyright. All rights reserved.
July 14, 2018: European Journal of Immunology
Maya Imbrechts, Karen De Samblancx, Karlien Fierens, Ellen Brisse, Jessica Vandenhaute, Tania Mitera, Claude Libert, Ide Smets, An Goris, Carine Wouters, Patrick Matthys
The production of IL-10, a potent immunosuppressive cytokine, must be strictly regulated to ensure a balanced immune response. IFN-γ, a key cytokine in multiple immune processes and pathologies, is known as an inhibitor of IL-10 production by monocytes and macrophages, but also has some regulatory functions. In the present study, we explored the role of IFN-γ on Toll-like receptor (TLR)-induced IL-10 production in murine peritoneal and spleen cells and in human peripheral blood mononuclear cells. IFN-γ inhibited IL-10 production induced by TLR2, TLR3, TLR4 and TLR7/8 agonists, but stimulated IL-10 production when cells were triggered with CpG oligodeoxynucleotides, a specific TLR9 agonist...
July 13, 2018: European Journal of Immunology
Jenny Voigt, David F G Malone, Joana Dias, Edwin Leeansyah, Niklas K Björkström, Hans-Gustaf Ljunggren, Lothar Gröbe, Frank Klawonn, Maxi Heyner, Johan K Sandberg, Lothar Jänsch
NK cells lacking CD56 (CD56neg ) were first identified in chronic HIV-1 infection. However, CD56neg NK cells also exist in healthy individuals, albeit in significantly lower numbers. Here, we provide an extensive proteomic characterisation of human CD56neg peripheral blood NK cells of healthy donors and compare them to their CD56dim and CD56bright counterparts. Unbiased large-scale surface receptor profiling clustered CD56neg cells as part of the main NK cell compartment and indicated an overall CD56dim -like phenotype...
July 12, 2018: European Journal of Immunology
Maiko Okumura, Tatsuhiko Ozawa, Hiroshi Hamana, Yu Norimatsu, Reina Tsuda, Eiji Kobayashi, Koichiro Shinoda, Hirofumi Taki, Kazuyuki Tobe, Johji Imura, Eiji Sugiyama, Hiroyuki Kishi, Atsushi Muraguchi
Anti-Ro52 autoantibodies (Ro52-autoAbs) appear in the sera of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Studies using patient sera have shown a correlation between the generation of Ro52-autoAbs and the clinical morbidity and severity of CTD with ILD. In this study, we used a single B-cell-manipulating technology and obtained twelve different monoclonal Ro52-autoAbs (mRo52-autoAbs) from the selected four patients suffering from severe ILD with a high titer of Ro52-autoAbs in their sera...
July 10, 2018: European Journal of Immunology
Yuko Horio, Koutaro Takamatsu, Daisuke Tamanoi, Ryo Sato, Koichi Saruwatari, Tokunori Ikeda, Shunya Nakane, Makoto Nakajima, Sho Saeki, Hidenori Ichiyasu, Kazuhiko Fujii, Yusuke Tomita
The complex interplay among cancer, host-immunity, and immunotherapy is not completely elucidated. Although studies have confirmed the association between cancer and hypercoagulopathy, a relationship between anti-programmed cell death-1 (PD-1) antibody therapy and thrombotic events remains unclear. Interferon-γ produced by activated T cells has been shown to be required for tissue factor synthesis in human monocytes/macrophages, suggesting activated of T cells by anti-PD-1 antibody therapy may lead to promote TF synthesis in monocytes/macrophages and trigger Trousseau's syndrome in cancer patients...
July 6, 2018: European Journal of Immunology
Tobias Alexander, Qingyu Cheng, Jens Klotsche, Laleh Khodadadi, Aderajew Waka, Robert Biesen, Bimba F Hoyer, Gerd R Burmester, Andreas Radbruch, Falk Hiepe
Long-lived plasma cells (PCs) not only provide protective humoral immunity, they are also an essential component of the autoreactive immunologic memory that may drive chronic immune responses in systemic autoimmunity, such as systemic lupus erythematosus (SLE). The therapeutic relevance of their targeting has been demonstrated in preclinical models and severe, treatment-refractory cases of autoimmune diseases using the proteasome inhibitor bortezomib. Herein we describe in detail the dynamic serologic changes and effects on immune effector cells in eight SLE patients receiving a median two cycles of 1...
July 6, 2018: European Journal of Immunology
Sascha Cording, Jasna Medvedovic, Emelyne Lecuyer, Tegest Aychek, François Dejardin, Gérard Eberl
Natural killer (NK) cells and lymphoid tissue inducer (LTi) cells were discovered more than 40 and 20 years ago, respectively. These two cell types were initially studied for their unique functions in the elimination of infected or transformed cells, and in the development of lymphoid tissues. It took an additional 10 years to realize that NK cells and LTi cells were members of a larger family of innate lymphoid cells (ILCs), whose phenotypes and functions mirror those of T cells. Many mouse models have since been developed to identify and isolate ILCs, map their developmental pathways and characterize their functions...
July 4, 2018: European Journal of Immunology
Guobao Chen, William Bracamonte-Baran, Nicola L Diny, Xuezhou Hou, Monica V Talor, Kai Fu, Yue Liu, Giovanni Davogustto, Hernan Vasquez, Heinrich Taegtmeyer, O Howard Frazier, Ari Waisman, Simon J Conway, Fengyi Wan, Daniela Čiháková
The causative effect of GM-CSF produced by cardiac fibroblasts to development of heart failure has not been shown. We identified the pathological GM-CSF-producing cardiac fibroblast subset and the specific deletion of IL-17A signaling to these cells attenuated cardiac inflammation and heart failure. We describe here the CD45- CD31- CD29+ mEF-SK4+ PDGFRα+ Sca-1+ periostin+ (Sca-1+ ) cardiac fibroblast subset as the main GM-CSF producer in both experimental autoimmune myocarditis and myocardial infarction mouse models...
June 28, 2018: European Journal of Immunology
Guan Wang, Ang Lin, Qiuju Han, Huajun Zhao, Zhigang Tian, Jian Zhang
Listeria monocytogenes (LM) is a foodborne Gram-positive intracellular pathogen that can cause listeriosis in humans and animals. Although phagocytes are known to be involved in the response to this infection, the role of neutrophils is not entirely clear. Here, we have demonstrated that soon after LM infection, a large number of IFN-γ-producing neutrophils quickly accumulated in the spleen, blood, and peritoneal cavity. Both in vivo and in vitro experiments demonstrated that neutrophils were an important source of IFN-γ...
June 23, 2018: European Journal of Immunology
Kouji Kobiyama, Melanie Vassallo, Jessica Mitzi, Holger Winkels, Hong Pei, Takayuki Kimura, Jacqueline Miller, Dennis Wolf, Klaus Ley
Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene oil similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA...
June 22, 2018: European Journal of Immunology
Rosemary E Morman, Patrick G Schweickert, Stephen F Konieczny, Elizabeth J Taparowsky
BATF functions in T cells and B cells to control the host response to antigen and promote the production of class switched immunoglobulins. In this study, we demonstrate that BATF expression increases rapidly, and transiently, following B cell stimulation and use an inducible murine model of BATF deletion to show that this induction is necessary, and sufficient, for immunoglobulin (Ig) class switch recombination (CSR). We examine two genes (Nfil3 and miR155gh) that are positively regulated, and one gene (Wnt10a) that is negatively regulated by BATF during CSR...
June 13, 2018: European Journal of Immunology
Stella Liong, Ratana Lim, Caitlyn Nguyen-Ngo, Gillian Barker, Helena C Parkington, Martha Lappas
There are currently no effective treatments to prevent spontaneous preterm labor. The precise upstream biochemical pathways that regulate the transition between uterine quiescence during pregnancy and contractility during labor remain unclear. It is well known however that intrauterine inflammation, including infection, is commonly associated with preterm labor. In this study, we identified the immunoproteasome subunit low-molecular-mass protein (LMP)7 mRNA expression to be significantly upregulated in laboring human myometrium...
June 8, 2018: European Journal of Immunology
Carolina V Gorlino, Mabel N Dave, Rodrigo Blas, María I Crespo, Alicia Lavanchy, Héctor Tamashiro, Rodolfo Pardo-Hildalgo, María C Pistoresi-Palencia, María S Di Genaro
Rheumatoid arthritis (RA) is characterized by the presence of anti-citrullinated peptide antibodies (ACPAs) and neutrophils infiltrating the synovial fluid (SF) of the affected joints. The aim of this work was to analyze whether the presence of ACPAs in SF is associated with neutrophil infiltration and with their phenotype in the inflamed joints of RA patients. We found that in the presence of ACPAs, the number of synovial neutrophils correlated with severe disease activity. The SF were divided according to synovial ACPA levels in negative- (<25 U/mL), low- (25-200 U/mL) and high level (˃200 U/mL; ACPAhigh )...
June 7, 2018: European Journal of Immunology
Anna E Boniakowski, Andrew S Kimball, Amrita Joshi, Matt Schaller, Frank M Davis, Aaron denDekker, Andrea T Obi, Bethany B Moore, Steve L Kunkel, Katherine A Gallagher
Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2-deficient mice (CCR2-/- ) demonstrate significantly impaired wound healing at all time points postinjury...
June 7, 2018: European Journal of Immunology
Qiong Jiang, Tingting Zhao, Wenhong Zheng, Jijun Zhou, Haoliang Wang, Hui Dong, Yongwen Chen, Xiaoqin Tang, Cong Liu, Lilin Ye, Qing Mao, Chunlin Wang, Jian Han, Xiaoyun Shang, Yuzhang Wu
The presence of shared T cell clonotypes was found in several different diseases, but its relationship with the progression of disease remains unclear. By sequencing the complementary determining region 3 of T cell receptor (TCR) β chains from the purified antigen-experienced CD8+ T cells, we characterized the T cell repertoire in a prospective cohort study among 75 patients with chronic hepatitis B in China, as well as a healthy control and a validation cohort. We found that most T cell clones from patients harbored the 'patient-specific' TCR sequences...
June 1, 2018: European Journal of Immunology
Rhys Jones, Emilie J Cosway, Claire Willis, Andrea J White, William E Jenkinson, Hans J Fehling, Graham Anderson, David R Withers
Members of the innate lymphoid cell (ILC) family have been implicated in the development of thymic microenvironments and the recovery of this architecture after damage. However, a detailed characterization of this family in the thymus is lacking. To better understand the thymic ILC compartment, we have utilized multiple in vivo models including the fate mapping of inhibitor of DNA binding-2 (Id2) expression and the use of Id2 reporter mice. Our data demonstrate that ILCs are more prominent immediately after birth, but were rapidly diluted as the T-cell development program increased...
May 31, 2018: European Journal of Immunology
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
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
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
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