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https://www.readbyqxmd.com/read/29781221/aberrant-expansion-and-function-of-t-follicular-helper-cell-subsets-in-igg4-related-disease
#1
Yu Chen, Wei Lin, Hongxian Yang, Mu Wang, Panpan Zhang, Ruie Feng, Hua Chen, Linyi Peng, Xuan Zhang, Yan Zhao, Xiaofeng Zeng, Fengchun Zhang, Wen Zhang, Peter E Lipsky
OBJECTIVE: To determine the number and function of Tfh cell subsets in IgG4-RD. METHODS: Mononuclear cells from peripheral blood and involved tissues of IgG4-RD patients were collected. Tfh cell subsets, mRNA levels of Bcl-6, Blimp-1 and IL-21 were tested. Immunohistochemistry and immunofluorescence techniques were used to assess the location of IL-21, Bcl-6, and (CD4+CXCR5+) Tfh cells in the involved tissues. Furthermore, by in vitro cell co-culture, the abilities of cTfh cell subsets to induce B cells proliferation, apoptosis, differentiation, and production of IgG4 were explored...
May 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29773681/decreased-expression-of-circulating-aire-and-increased-tfh-tfr-cells-in-myasthenia-gravis-patients
#2
Sijia Zhao, Jiaqi Ding, Shengyuan Wang, Chuan Li, Peng Guo, Min Zhang, Zhuyi Li
Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of Autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells(we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T follicular helper (cTfh) and T follicular regulatory (cTfr) cells in MG patients...
May 17, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29769448/tlr-adjuvanted-nanoparticle-vaccines-differentially-influence-the-quality-and-longevity-of-responses-to-malaria-antigen-pfs25
#3
Elizabeth A Thompson, Sebastian Ols, Kazutoyo Miura, Kelly Rausch, David L Narum, Mats Spångberg, Michal Juraska, Ulrike Wille-Reece, Amy Weiner, Randall F Howard, Carole A Long, Patrick E Duffy, Lloyd Johnston, Conlin P O'Neil, Karin Loré
Transmission-blocking vaccines (TBVs) are considered an integral element of malaria eradication efforts. Despite promising evaluations of Plasmodium falciparum Pfs25-based TBVs in mice, clinical trials have failed to induce robust and long-lived Ab titers, in part due to the poorly immunogenic nature of Pfs25. Using nonhuman primates, we demonstrate that multiple aspects of Pfs25 immunity were enhanced by antigen encapsulation in poly(lactic-co-glycolic acid)-based [(PLGA)-based] synthetic vaccine particles (SVP[Pfs25]) and potent TLR-based adjuvants...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#4
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29768737/providence-of-cd25-kir-cd127-foxp3-cd8-t-cell-subset-determines-the-dynamics-of-tumor-immune-surveillance
#5
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29757907/t-follicular-regulatory-cells-and-antibody-responses-in-transplantation
#6
E F Wallin
De novo donor specific antibody (DSA) formation is a major problem in transplantation, and associated with long-term graft decline and loss as well as sensitisation, limiting future transplant options. Forming high-affinity, long-lived antibody responses involves a process called the germinal center (GC) reaction, and requires interaction between several cell types, including GC B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Tfr cells are an essential component of the GC reaction, limiting its size and reducing nonspecific or self-reactive responses...
May 1, 2018: Transplantation
https://www.readbyqxmd.com/read/29743364/t-cell-derived-lymphotoxin-is-essential-for-anti-hsv-1-humoral-immune-response
#7
Kaiting Yang, Yong Liang, Zhichen Sun, Diyuan Xue, Hairong Xu, Mingzhao Zhu, Yang-Xin Fu, Hua Peng
B cell-derived lymphotoxin (LT) is required for the development of follicular dendritic cell clusters for the formation of primary and secondary lymphoid follicles, but the role of T cell-derived LT in antibody response has not been well demonstrated. We observed that lymphotoxin-β-receptor (LTβR) signaling is essential for optimal humoral immune response and protection against an acute HSV-1 infection. Blocking the LTβR pathway caused poor maintenance of germinal center B (GC-B) cells and follicular helper T (Tfh) cells...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743314/cd8-follicular-t-cells-promote-b-cell-antibody-class-switch-in-autoimmune-disease
#8
Kristen M Valentine, Dan Davini, Travis J Lawrence, Genevieve N Mullins, Miguel Manansala, Mufadhal Al-Kuhlani, James M Pinney, Jason K Davis, Anna E Beaudin, Suzanne S Sindi, David M Gravano, Katrina K Hoyer
CD8 T cells can play both a protective and pathogenic role in inflammation and autoimmune development. Recent studies have highlighted the ability of CD8 T cells to function as T follicular helper (Tfh) cells in the germinal center in the context of infection. However, whether this phenomenon occurs in autoimmunity and contributes to autoimmune pathogenesis is largely unexplored. In this study, we show that CD8 T cells acquire a CD4 Tfh profile in the absence of functional regulatory T cells in both the IL-2-deficient and scurfy mouse models...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29739909/a-high-frequency-of-hiv-specific-circulating-follicular-helper-t-cells-is-associated-with-preserved-memory-b-cell-responses-in-hiv-controllers
#9
M Claireaux, M Galperin, D Benati, A Nouël, M Mukhopadhyay, J Klingler, P de Truchis, D Zucman, S Hendou, F Boufassa, C Moog, O Lambotte, L A Chakrabarti
Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4+ T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet+ ), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA- CXCR5+ CD4+ T cell population, proved more frequent in the controller group ( P = 0...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29739835/nucleoside-modified-mrna-vaccines-induce-potent-t-follicular-helper-and-germinal-center-b-cell-responses
#10
Norbert Pardi, Michael J Hogan, Martin S Naradikian, Kaela Parkhouse, Derek W Cain, Letitia Jones, M Anthony Moody, Hans P Verkerke, Arpita Myles, Elinor Willis, Celia C LaBranche, David C Montefiori, Jenna L Lobby, Kevin O Saunders, Hua-Xin Liao, Bette T Korber, Laura L Sutherland, Richard M Scearce, Peter T Hraber, István Tombácz, Hiromi Muramatsu, Houping Ni, Daniel A Balikov, Charles Li, Barbara L Mui, Ying K Tam, Florian Krammer, Katalin Karikó, Patricia Polacino, Laurence C Eisenlohr, Thomas D Madden, Michael J Hope, Mark G Lewis, Kelly K Lee, Shiu-Lok Hu, Scott E Hensley, Michael P Cancro, Barton F Haynes, Drew Weissman
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates...
May 8, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29732234/microrna-mediated-regulation-of-the-development-and-functions-of-follicular-helper-t-cells
#11
REVIEW
Jeonghyun Lee, Hyosung Park, Jiyoung Eom, Seung Goo Kang
The germinal center reaction is a key event of humoral immunity, providing long-lived immunological memory. Follicular helper T (TFH ) cells are a specialized subset of CD4+ T cells located in the follicles, which help B cells and thus control the germinal center reaction. TFH cell development is achieved by multi-step processes of interactions with dendritic cells and B cells along with the coordination of various transcription factors. Since the T helper cell fate decision program is determined by subtle changes in regulatory molecules, fine tuning of these dynamic interactions is crucial for the generation functional TFH cells...
April 2018: Immune Network
https://www.readbyqxmd.com/read/29731839/high-frequency-of-circulating-follicular-helper-t-cells-is-correlated-with-b-cell-subtypes-in-patients-with-ankylosing-spondylitis
#12
Siqi Long, Li Ma, Dongsheng Wang, Xianwen Shang
T follicular helper (Tfh) cells are known to support effector B cells and enhance autoimmunity; however, the association between the Tfh cells and B cells in ankylosing spondylitis (AS) is unclear. The aim of the present study was to measure the frequency of circulating cluster of differentiation (CD)4+ C-X-C chemokine receptor type 5 (CXCR5)+ Tfh cells and B cell subtypes in peripheral blood from patients with AS, and evaluate the correlation of these factors. Percentages of peripheral blood circulating CD4+ CXCR5+ Tfh cells and B cell subtypes were measured via flow cytometry and the disease activity of individual patients was measured using the Bath AS Disease Activity Index (BASDAI)...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29728406/b-cell-differentiation-and-il-21-response-in-il2rg-jak3-scid-patients-after-hematopoietic-stem-cell-transplantation
#13
Alexandra M Miggelbrink, Brent R Logan, Rebecca H Buckley, Roberta E Parrott, Christopher C Dvorak, Neena Kapoor, Hisham Abdel-Azim, Susan E Prockop, David Shyr, Hélène Decaluwe, Imelda C Hanson, Alfred Gillio, Blachy J Dávila Saldaña, Hermann Eibel, Gregory Hopkins, Jolan E Walter, Jennifer S Whangbo, Donald B Kohn, Jennifer M Puck, Morton J Cowan, Linda M Griffith, Elie Haddad, Richard J O'Reilly, Luigi D Notarangelo, Sung-Yun Pai
Allogeneic hematopoietic stem cell transplant (HSCT) typically results in donor T cell engraftment and function in patients with severe combined immunodeficiency (SCID), but humoral immunity, particularly when using donors other than matched siblings, is variable. B cell function after HSCT for SCID depends on the genetic cause, the use of pre-HSCT conditioning and whether donor B cell chimerism is achieved. Patients with defects in IL2RG or JAK3 undergoing HSCT without conditioning often have poor B cell function post-HSCT, perhaps due to impairment of IL-21 signaling in host-derived B cells...
May 4, 2018: Blood
https://www.readbyqxmd.com/read/29718303/the-kdm4a-kdm4c-nf-%C3%AE%C2%BAb-and-wdr5-epigenetic-cascade-regulates-the-activation-of-b-cells
#14
Kuo-Hsuan Hung, Yong H Woo, I-Ying Lin, Chin-Hsiu Liu, Li-Chieh Wang, Hsin-Yu Chen, Bor-Luen Chiang, Kuo-I Lin
T follicular helper (Tfh) cell-derived signals promote activation and proliferation of antigen-primed B cells. It remains unclear whether epigenetic regulation is involved in the B cell responses to Tfh cell-derived signals. Here, we demonstrate that Tfh cell-mimicking signals induce the expression of histone demethylases KDM4A and KDM4C, and the concomitant global down-regulation of their substrates, H3K9me3/me2, in B cells. Depletion of KDM4A and KDM4C potentiates B cell activation and proliferation in response to Tfh cell-derived signals...
April 30, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29713015/atherogenic-dyslipidemia-promotes-autoimmune-follicular-helper-t-cell-responses-via-il-27
#15
Heeju Ryu, Hoyong Lim, Garam Choi, Young-Jun Park, Minkyoung Cho, Hyeongjin Na, Chul Won Ahn, Young Chul Kim, Wan-Uk Kim, Sang-Hak Lee, Yeonseok Chung
The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe-/- and Ldlr-/- mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3+ follicular helper T cells (TFH cells). TFH cells isolated from Apoe-/- mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c...
April 30, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29705247/transfer-of-gene-corrected-t-cells-corrects-humoral-and-cytotoxic-defects-in-x-linked-lymphoproliferative-disease-xlp1
#16
Neelam Panchal, Ben Houghton, Begona Diez, Sujal Ghosh, Ida Ricciardelli, Adrian J Thrasher, H Bobby Gaspar, Claire Booth
BACKGROUND: XLP1 arises from mutations in the SH2D1A gene encoding SAP, an adaptor protein expressed in T, NK and NKT cells. Defects lead to abnormalities of T and NK cell cytotoxicity and T cell dependent humoral function. Clinical manifestations include haemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinaemia. Curative treatment is limited to haematopoietic stem cell transplant with outcome reliant on a good donor match. OBJECTIVES: As most symptoms arise from defective T cell function, we investigated whether transfer of SAP gene corrected T cells could reconstitute known effector cell defects...
April 26, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29705243/a-kindred-with-mutant-ikaros-and-autoimmunity
#17
Erika Van Nieuwenhove, Josselyn E Garcia-Perez, Christine Helsen, Princess D Rodriguez, Pauline A van Schouwenburg, James Dooley, Susan Schlenner, Mirjam van der Burg, Els Verhoeyen, Rik Gijsbers, Seth Frietze, Hilde Schjerven, Isabelle Meyts, Frank Claessens, Stephanie Humblet-Baron, Carine Wouters, Adrian Liston
IKAROS (encoded by IKZF1) is an important hematopoietic transcription factor critical for early B cell differentiation, with major defects known to lead to low B cell numbers and hypogammaglobulinemia. More perplexing is the link between IKZF1 variants and autoimmunity, including polymorphisms associated with susceptibility to SLE, and recently, rare variants driving monogenic autoimmunity. We identified a novel p.L188V mutation in IKZF1 in the index patient and her father and found this mutation to lead to loss of DNA binding...
April 26, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29704593/treg-dysfunction-induces-autoantibodies-to-bullous-pemphigoid-antigens-in-mice-and-humans
#18
Ken Muramatsu, Hideyuki Ujiie, Ichiro Kobayashi, Wataru Nishie, Kentaro Izumi, Takamasa Ito, Norihiro Yoshimoto, Ken Natsuga, Hiroaki Iwata, Hiroshi Shimizu
BACKGROUND: Regulatory T cells (Tregs) play a crucial role in peripheral immune tolerance in multiple organs, including the skin. Thus far, the impact of peripheral immune tolerance failure on autoantibody-related autoimmune reaction to the skin is unclear. OBJECTIVE: We sought to elucidate the target autoantigens in the skin under the condition of Treg dysfunction due to Foxp3 gene mutations in scurfy mice and patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome...
April 25, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29698707/distinct-characteristics-of-hippocampal-pathogenic-t-h-17-cells-in-a-mouse-model-of-depression
#19
Eléonore Beurel, Jeffrey Lowell, Richard Jope
Increasing evidence indicates that multiple actions of the immune system are closely intertwined with the development of depression and subsequent recovery processes. One of these interactions is substantial evidence that the TH 17 subtype of CD4+ T cells promotes susceptibility to depression-like behaviors in rodents. Comparing subtypes of CD4+ T cells, we found that administration of TH 17 cells, but not TH 1 cells or TREGS , promoted susceptibility to learned-helplessness depressive-like behavior and accumulated in the hippocampus of learned helpless mice...
April 23, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29694256/associations-of-circulating-cxcr3-pd-1-cd4-t-cells-with-disease-activity-of-systemic-lupus-erythematosus
#20
Han Lei, Yang Xue, Yu Yiyun, Wan Weiguo, Lv Ling, Hejian Zou
OBJECTIVES: Which helper CD4+ T cell subset contributes to autoantibodies generation and severity of end-organ involvement in lupus patients remains to be explored. Our research aims to investigate the roles of circulating Tfh (cTfh) cell subsets and corresponding CXCR5- Th cells in lupus patients and their correlation with SLEDAI. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from blood of SLE patients as well as healthy donors. The proportion of Th cell Subsets classified from cell surface markers (CD45RO, CXCR5, CXCR3, CCR6, PD-1, ICOS, and CCR7) is detected by flow cytometry...
April 25, 2018: Modern Rheumatology
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