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Follicular helper T cells

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https://www.readbyqxmd.com/read/28943543/expression-of-master-regulators-of-t-cell-helper-t-cell-and-follicular-helper-t-cell-differentiation-in-angioimmunoblastic-t-cell-lymphoma
#1
Yosuke Matsumoto, Hisao Nagoshi, Mihoko Yoshida, Seiichi Kato, Junya Kuroda, Kazuho Shimura, Hiroto Kaneko, Shigeo Horiike, Shigeo Nakamura, Masafumi Taniwaki
Objective It has been postulated that the normal counterpart of angioimmunoblastic T-cell lymphoma (AITL) is the follicular helper T-cell (TFH). Recent immunological studies have identified several transcription factors responsible for T-cell differentiation. The master regulators associated with T-cell, helper T-cell (Th), and TFH differentiation are reportedly BCL11B, Th-POK, and BCL6, respectively. We explored the postulated normal counterpart of AITL with respect to the expression of the master regulators of T-cell differentiation...
September 25, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28941291/dysregulation-of-circulating-tfr-tfh-ratio-in-primary-biliary-cholangitis
#2
Jiajia Zheng, Tiancheng Wang, Li Zhang, Liyan Cui
Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are critical for the development and maintenance of germinal center (GC) and humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of either Tfh cells or Tfr cells contributes to the pathogenesis of autoimmune diseases. We aim to investigate the roles of circulating Tfh cells and circulating Tfr cells in the pathogenesis of primary biliary cholangitis (PBC). 34 PBC patients and 27 health individuals were enrolled in this study...
September 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28939548/icams-support-b-cell-interactions-with-t-follicular-helper-cells-and-promote-clonal-selection
#3
Irina Zaretsky, Ofir Atrakchi, Roei D Mazor, Liat Stoler-Barak, Adi Biram, Sara W Feigelson, Alexander D Gitlin, Britta Engelhardt, Ziv Shulman
The germinal center (GC) reaction begins with a diverse and expanded group of B cell clones bearing a wide range of antibody affinities. During GC colonization, B cells engage in long-lasting interactions with T follicular helper (Tfh) cells, a process that depends on antigen uptake and antigen presentation to the Tfh cells. How long-lasting T-B interactions and B cell clonal expansion are regulated by antigen presentation remains unclear. Here, we use in vivo B cell competition models and intravital imaging to examine the adhesive mechanisms governing B cell selection for GC colonization...
September 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28938496/icaritin-improves-antibody-induced-thrombocytopenia-in-a-mouse-model-by-regulating-t-cell-polarization
#4
Chenghong Sun, Jian Yang, Mingzhi Wang, Lihong Pan, Jingchun Yao, Shenglan Wang, Na Guo, Chunyan Li, Guimin Zhang
Previous studies have shown that icaritin (ICT) has significant protective effects on immune thrombocytopenia (ITP), and the present study aimed to discuss the mechanism of this protective effect from the aspect of regulating T-cell polarization by an antibody-induced ITP mice model. Mice were given rat anti-mouse CD41 antibody (MWReg30) by intraperitoneal injection for 7 d to produce ITP model. At the same time, ICT was administrated at 10 mg/kg/d orally for 9 d. Peripheral blood platelets were counted by hematology analyzer...
September 22, 2017: Planta Medica
https://www.readbyqxmd.com/read/28935714/profiling-mhc-ii-immunopeptidome-of-blood-stage-malaria-reveals-that-cdc1-control-the-functionality-of-parasite-specific-cd4-t-cells
#5
Marion Draheim, Myriam F Wlodarczyk, Karine Crozat, Jean-Michel Saliou, Tchilabalo Dilezitoko Alayi, Stanislas Tomavo, Ali Hassan, Anna Salvioni, Claudia Demarta-Gatsi, John Sidney, Alessandro Sette, Marc Dalod, Antoine Berry, Olivier Silvie, Nicolas Blanchard
In malaria, CD4 Th1 and T follicular helper (TFH) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins...
September 21, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28933361/lysosomal-storage-disorders-and-malignancy
#6
REVIEW
Gregory M Pastores, Derralynn A Hughes
Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells...
February 27, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28930662/the-kinase-mtorc1-promotes-the-generation-and-suppressive-function-of-follicular-regulatory-t-cells
#7
Lifan Xu, Qizhao Huang, Haoqiang Wang, Yaxing Hao, Qiang Bai, Jianjun Hu, Yiding Li, Pengcheng Wang, Xiangyu Chen, Ran He, Bingshou Li, Xia Yang, Tingting Zhao, Yanyan Zhang, Yifei Wang, Juanjuan Ou, Houjie Liang, Yuzhang Wu, Xinyuan Zhou, Lilin Ye
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28916523/cutting-edge-a-critical-role-of-lesional-t-follicular-helper-cells-in-the-pathogenesis-of-igg4-related-disease
#8
Ryuta Kamekura, Kenichi Takano, Motohisa Yamamoto, Koji Kawata, Katsunori Shigehara, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Akinori Sato, Noriko Ogasawara, Chieko Tsubomatsu, Hiroki Takahashi, Hiroshi Nakase, Tetsuo Himi, Shingo Ichimiya
IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing programmed death 1 and ICOS in submandibular glands. Tfh cells from IgG4-DS submandibular glands had higher expression of B cell lymphoma 6 and a greater capacity to help B cells produce IgG4 than did tonsillar Tfh cells...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28916434/effects-of-icos-t-cell-depletion-via-afucosylated-monoclonal-antibody-medi-570-on-pregnant-cynomolgus-monkeys-and-the-developing-offspring
#9
Simone M Nicholson, Gianluca Carlesso, Lily I Cheng, Halie Cook, Karma DaCosta, Joel Leininger, Kathleen McKeever, Stephen Weasel Scott, Devon Taylor, Katie Streicher, Steve Eck, Molly Reed, Raffaella Faggioni, Ronald Herbst, Rakesh Dixit, Patricia C Ryan
MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did cause any abortifacient effects. Changes in hematology and peripheral blood T lymphocyte subsets in maternal animals and infants and the attenuated infant IgG immune response to keyhole limpet hemocyanin (KLH) were attributed to MEDI-570 pharmacology...
September 12, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28899868/b-cell-derived-il-6-initiates-spontaneous-germinal-center-formation-during-systemic-autoimmunity
#10
Tanvi Arkatkar, Samuel W Du, Holly M Jacobs, Elizabeth M Dam, Baidong Hou, Jane H Buckner, David J Rawlings, Shaun W Jackson
Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell-derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed...
September 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28892471/dynamic-regulation-of-t-follicular-regulatory-cell-responses-by-interleukin-2-during-influenza-infection
#11
Davide Botta, Michael J Fuller, Tatiana T Marquez-Lago, Holly Bachus, John E Bradley, Amy S Weinmann, Allan J Zajac, Troy D Randall, Frances E Lund, Beatriz León, André Ballesteros-Tato
Interleukin 2 (IL-2) promotes Foxp3(+) regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some Treg cells downregulated CD25, upregulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones...
September 11, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28892065/regulatory-t-cells-impede-acute-and-long-term-immunity-to-blood-stage-malaria-through-ctla-4
#12
Samarchith P Kurup, Nyamekye Obeng-Adjei, Scott M Anthony, Boubacar Traore, Ogobara K Doumbo, Noah S Butler, Peter D Crompton, John T Harty
Malaria, caused by the protozoan Plasmodium, is a devastating mosquito-borne disease with the potential to affect nearly half the world's population. Despite mounting substantial T and B cell responses, humans fail to efficiently control blood-stage malaria or develop sterilizing immunity to reinfections. Although forkhead box P3 (FOXP3)(+)CD4(+) regulatory T (Treg) cells form a part of these responses, their influence remains disputed and their mode of action is unknown. Here we show that Treg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (TFH)-B cell interactions in germinal centers...
September 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28888925/follicular-helper-t-cells-are-essential-for-the-elimination-of-plasmodium-infection
#13
Damián Pérez-Mazliah, Minh Phuong Nguyen, Caroline Hosking, Sarah McLaughlin, Matthew D Lewis, Irene Tumwine, Prisca Levy, Jean Langhorne
CD4(+) follicular helper T (Tfh) cells have been shown to be critical for the activation of germinal center (GC) B-cell responses. Similar to other infections, Plasmodium infection activates both GC as well as non-GC B cell responses. Here, we sought to explore whether Tfh cells and GC B cells are required to eliminate a Plasmodium infection. A CD4 T cell-targeted deletion of the gene that encodes Bcl6, the master transcription factor for the Tfh program, resulted in complete disruption of the Tfh response to Plasmodium chabaudi in C57BL/6 mice and consequent disruption of GC responses and IgG responses and the inability to eliminate the otherwise self-resolving chronic P...
September 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28888664/regulatory-t-cells-and-tlr9-activation-shape-antibody-formation-to-a-secreted-transgene-product-in-aav-muscle-gene-transfer
#14
Roland W Herzog, Mario Cooper, George Q Perrin, Moanaro Biswas, Ashley T Martino, Laurence Morel, Cox Terhorst, Brad E Hoffman
Adeno-associated viral (AAV) gene delivery to skeletal muscle is being explored for systemic delivery of therapeutic proteins. To better understand the signals that govern antibody formation against secreted transgene products in this approach, we administered an intramuscular dose of AAV1 vector expressing human coagulation factor IX (hFIX), which does not cause antibody formation against hFIX in C57BL/6 mice. Interestingly, co-administration of a TLR9 agonist (CpG-deoxyoligonucleotide, ODN) but not of lipopolysaccharide, caused a transient anti-hFIX response...
August 1, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28887367/tfr-cells-lack-il-2r%C3%AE-but-express-decoy-il-1r2-and-il-1ra-and-suppress-the-il-1-dependent-activation-of-tfh-cells
#15
Paul-Gydeon G Ritvo, Guillame Churlaud, Valentin Quiniou, Laura Florez, Faustine Brimaud, Gwladys Fourcade, Encarnita Mariotti-Ferrandiz, David Klatzmann
Follicular regulatory T (Tfr) cells from lymph node germinal centers control follicular helper T (Tfh) cell-dependent B cell activation. These scarce cells, often described and purified as CD25(+) cells, are thought to be derived from thymic regulatory T (Treg) cells. However, we observed that mouse Tfr cells do not respond to interleukin-2 (IL-2), unlike Treg cells. Stringent immunophenotyping based on B cell lymphoma 6 (Bcl6), programmed cell death protein 1 (PD-1), and CXCR5 expression revealed that Tfr cells are actually CD25(-), in mice and humans...
September 8, 2017: Science Immunology
https://www.readbyqxmd.com/read/28885497/influence-of-the-novel-atp-competitive-dual-mtorc1-2-inhibitor-azd2014-on-immune-cell-populations-and-heart-allograft-rejection
#16
Daniel Fantus, Helong Dai, Yoshihiro Ono, Alicia Watson, Shinichiro Yokota, Kanishka Mohib, Osamu Yoshida, Mark A Ross, Simon C Watkins, Bala Ramaswami, Anna Valusjkikh, David M Rothstein, Angus W Thomson
BACKGROUND: Little is known about how new generation adenosine triphosphate (ATP)-competitive mechanistic target of rapamycin (mTOR) kinase inhibitors (TORKinibs) affect immunity and allograft rejection. METHODS: mTOR complex (C) 1 and 2 signaling in dendritic cells (DC) and T cells was analyzed by Western blotting, while immune cell populations in normal and heart allograft recipient mice were analyzed by flow cytometry. Alloreactive T cell proliferation was quantified in MLR; intracellular cytokine production and serum antidonor IgG levels were determined by flow analysis and immunofluorescence staining used to detect IgG in allografts...
September 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28881401/generation-of-t-follicular-helper-cells-in-vitro-requirement-for-bcr-cross-linking-and-cognate-b-and-t-cell-interaction
#17
Anne Kolenbrander, Bastian Grewe, David Nemazee, Klaus Überla, Vladimir Temchura
The minimal requirements for in vitro modeling of the natural CD4(+) T-cell differentiation into T follicular helper (TFH) cells are still under investigation. We co-cultured wild type and TCR-transgenic CD4(+) T-cells from naïve mice with dendritic cells and BCR-transgenic B-cells in the presence of HIV-derived virus-like particles containing matched B- and T-cell epitopes. This co-culturing induced co-expression of TFH-master regulator transcription factor BCL-6 and CXCR5 in up to 10% of the wild type and up to 40% of the TCR-transgenic CD4(+) T-cells...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28879521/fcrla-a-resident-endoplasmic-reticulum-protein-that-associates-with-multiple-immunoglobulin-isotypes-in-b-lineage-cells
#18
Tessa E Blackburn, Teresa Santiago, Peter D Burrows
FCRLA is homologous to receptors for the Fc portion of IgG (FcγR) and is located in the same region of human chromosome one, but has several unusual and unique features. It is a soluble resident ER protein retained in this organelle by unknown mechanisms involving the N-terminal domain, a disordered domain with three Cys residues in close proximity in the human protein. Unlike the FcγRs, FCRLA is not glycosylated and has no transmembrane region. FCRLA is included in this CTMI volume on IgM-binding proteins because it binds IgM in the ER, but quite surprisingly, given the isotype-restricted ligand specificity of the other FcRs, it also binds all other Ig isotypes so far tested, IgG and IgA...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28878083/how-germinal-centers-evolve-broadly-neutralizing-antibodies-the-breadth-of-the-follicular-helper-t-cell-response
#19
Rob J De Boer, Alan S Perelson
Many HIV-1 infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years, and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest affinity receptors tend to acquire the most antigen from the FDC network, and present the highest density of cognate peptides to follicular helper T cells (Tfh), which provide survival signals to the B cell. BnAbs are therefore only expected to evolve when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than other lineages of more specific B cells...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28876451/selective-hdac6-inhibition-decreases-early-stage-of-lupus-nephritis-by-downregulating-both-innate-and-adaptive-immune-responses
#20
Jingjing Ren, Xiaofeng Liao, Miranda D Vieson, Miao Chen, Reilly Scott, Jillian Kazmierczak, Xin M Luo, Christopher M Reilly
We have previously demonstrated that HDAC6 expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) NZB/W F1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for five weeks...
September 6, 2017: Clinical and Experimental Immunology
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