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Follicular helper T cells

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https://www.readbyqxmd.com/read/27923906/cd4-t-cell-effector-commitment-coupled-to-self-renewal-by-asymmetric-cell-divisions
#1
Simone A Nish, Kyra D Zens, Radomir Kratchmarov, Wen-Hsuan W Lin, William C Adams, Yen-Hua Chen, Bonnie Yen, Nyanza J Rothman, Avinash Bhandoola, Hai-Hui Xue, Donna L Farber, Steven L Reiner
Upon infection, an activated CD4(+) T cell produces terminally differentiated effector cells and renews itself for continued defense. In this study, we show that differentiation and self-renewal arise as opposing outcomes of sibling CD4(+) T cells. After influenza challenge, antigen-specific cells underwent several divisions in draining lymph nodes (LN; DLNs) while maintaining expression of TCF1. After four or five divisions, some cells silenced, whereas some cells maintained TCF1 expression. TCF1-silenced cells were T helper 1-like effectors and concentrated in the lungs...
December 6, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27921272/bcl6-locus-is-hypermethylated-in-angioimmunoblastic-t-cell-lymphoma
#2
Shoko Nishizawa, Mamiko Sakata-Yanagimoto, Keiichiro Hattori, Hideharu Muto, Tran Nguyen, Koji Izutsu, Kenichi Yoshida, Seishi Ogawa, Naoya Nakamura, Shigeru Chiba
BCL6, a master transcription factor for differentiation of follicular helper T (TFH) cells, is highly expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL) containing tumor cells with TFH features. TET2, encoding an epigenetic regulator, is frequently mutated in AITL/PTCL. We previously reported that Tet2 knockdown mice developed T-cell lymphomas with TFH features. Hypermethylation of the Bcl6 locus followed by BCL6 upregulation was thought to be the key event for lymphoma development in mice...
December 5, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27920778/the-dynamics-of-t-and-b-cells-in-lymph-node-during-chronic-hiv-infection-tfh-and-hiv-unhappy-dance-partners
#3
REVIEW
Jung Joo Hong, Kyu-Tae Chang, Francois Villinger
Although the dynamics of germinal center (GC) formation, follicular helper T (TFH) cell recruitment to B cell follicles within lymphoid organs, and changes of lymphoid tissue architecture in HIV/SIV infection have been documented, the underlying immunopathology remains unclear. Here, we summarize what is known regarding the kinetics of TFH cells and GC B cells during the course of infection as well as the potential immunopathological features associated with structural changes in the lymphoid compartment. This review also explores the implications of cell dynamics in the formation and maintenance of viral reservoirs in hyperplastic follicles of secondary lymphoid organs before and after viral suppressive antiretroviral therapy...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27920023/il4-from-t-follicular-helper-cells-downregulates-antitumor-immunity
#4
Hidekazu Shirota, Dennis M Klinman, Shuku-Ei Ito, Hiroyasu Ito, Masato Kubo, Chikashi Ishioka
Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the LNs...
December 5, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27919633/greater-activation-of-peripheral-t-follicular-helper-cells-following-high-dose-influenza-vaccine-in-older-adults-forecasts-seroconversion
#5
Mark A Pilkinton, Katherine J Nicholas, Christian M Warren, Rita M Smith, Sandra M Yoder, H Keipp Talbot, Spyros A Kalams
BACKGROUND: Influenza related morbidity and mortality disproportionately impacts older adults. The serologic response to vaccine is diminished in older adults; however, high dose inactivated influenza vaccine (HD IIV) has shown improved rates of seroconversion compared to standard dose (SD IIV). We hypothesize this may be due to the superior ability of high dose vaccine to activate T follicular helper (Tfh) cells and provide B cell dependent T cell help. METHODS: We measured peripheral Tfh (pTfh) activation in 50 community dwelling adults 65years or older who were randomly assigned to receive either the HD IIV or SD IIV...
December 2, 2016: Vaccine
https://www.readbyqxmd.com/read/27913516/immunoregulatory-networks-in-sickle-cell-alloimmunization
#6
Karina Yazdanbakhsh
Red blood cell (RBC) transfusions are critical for treatment and prevention of complications of sickle cell disease (SCD), and most SCD patients will receive 1 or more transfusions by age 20. However, SCD alloimmunization remains a serious complication of transfusions that can lead to life-threatening acute and delayed transfusion reactions. Alloimmunization rates are higher in SCD patients most likely due to RBC antigenic differences between largely white donors vs mainly African-American recipients and frequency of transfusions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#7
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27908305/abatacept-treatment-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-results-in-a-decrease-of-germinal-centres-in-salivary-gland-tissue
#8
Erlin A Haacke, Bert van der Vegt, Petra M Meiners, Arjan Vissink, Fred K L Spijkervet, Hendrika Bootsma, Frans G M Kroese
OBJECTIVES: The aim of this study was to assess the histopathological changes in parotid gland tissue of primary Sjögren's syndrome (pSS) patients treated with abatacept. METHODS: In all 15 pSS patients included in the open-label Active Sjögren Abatacept Pilot (ASAP, 8 abatacept infusions) study parotid gland biopsies were taken before treatment and at 24 weeks of follow up. Biopsies were analysed for pSS-related histopathological features and placed in context of clini- cal responsiveness as assessed with EULAR Sjögren's syndrome disease activity index (ESSDAI)...
November 12, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27902353/corrigendum-to-follicular-helper-t-cells-and-virus-specific-antibody-response-in-primary-and-reactivated-human-cytomegalovirus-infections-of-the-immunocompetent-and-immunocompromised-transplant-patients
#9
Francesca Bruno, Chiara Fornara, Paola Zelini, Milena Furione, Elena Carrara, Lucia Scaramuzzi, Ilaria Cane, Federico Mele, Federica Sallusto, Daniele Lilleri, Giuseppe Gerna
No abstract text is available yet for this article.
October 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902338/recombinant-rabies-virus-expressing-il-21-enhances-immunogenicity-through-activation-of-t-follicular-helper-cells-and-germinal-center-b-cells
#10
Yajing Zhang, Ming Zhou, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao
Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signaling could affect specific antibody induction after rabies vaccination. Here, to further investigate the overexpression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated as LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that mice immunized with LBNSE-IL21 could substantially increase the number of T follicular helper (Tfh) cells and germinal center (GC) B cells but did not enhance dendritic cell (DC) activation...
October 25, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#11
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
November 26, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27897259/artemisinin-analogue-sm934-attenuate-collagen-induced-arthritis-by-suppressing-t-follicular-helper-cells-and-t-helper-17-cells
#12
Ze-Min Lin, Xiao-Qian Yang, Feng-Hua Zhu, Shi-Jun He, Wei Tang, Jian-Ping Zuo
SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895177/ox40-cooperates-with-icos-to-amplify-follicular-th-cell-development-and-germinal-center-reactions-during-infection
#13
Vikas Tahiliani, Tarun E Hutchinson, Georges Abboud, Michael Croft, Shahram Salek-Ardakani
Cognate interactions between T follicular helper (Tfh) cells and B cells are essential for promoting protective Ab responses. Whereas costimulatory receptors such as ICOS are accepted as being important for the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the Tfh phenotype. In this study, with vaccinia virus infection in mice, we show that OX40 was expressed on Tfh cells that accumulated at the T/B borders in the white pulp of the spleen and that OX40-dependent signals directly shaped the magnitude and quality of the their response to viral Ags...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27891132/impact-of-chronic-hiv-siv-infection-on-t-follicular-helper-cell-subsets-and-germinal-center-homeostasis
#14
REVIEW
Stéphanie Graff-Dubois, Angeline Rouers, Arnaud Moris
The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has renewed optimism for developing an effective vaccine against HIV-1. The generation of most bNAbs requires multiple rounds of B cell receptor affinity maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their production. However, less than 1% of HIV-infected patients develop bNAbs that arise late in the course of infection, indicating probable Tfh and B cell dysfunctions in this context. Since the last few years, many studies have characterized Tfh cells from lymph nodes and spleen of HIV-infected individuals and SIV-infected macaques...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27888555/renal-operational-tolerance-is-associated-with-a-defect-of-blood-tfh-cells-that-exhibit-impaired-b-cell-help
#15
Alexis Chenouard, Mélanie Chesneau, Linh Bui Nguyen, Sabine Le Bot, Marion Cadoux, Emilie Dugast, Chloé Paul, Stéphanie Malard-Castagnet, Simon Ville, Pierrick Guérif, Jean-Paul Soulillou, Nicolas Degauque, Richard Danger, Magali Giral, Sophie Brouard
Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper cells (Tfh) play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh from TOL displayed a modified gene expression profile, failed to produce IL-21 and were unable to induce IgG production by naive B cells...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27888017/circulating-cxcr5-cd4-t-cells-assist-in-the-survival-and-growth-of-primary-diffuse-large-b-cell-lymphoma-cells-through-interleukin-10-pathway
#16
Zhanshan Cha, Guangfang Qian, Yan Zang, Haihui Gu, Yanyan Huang, Lishuang Zhu, Jinqi Li, Yang Liu, Xiaohua Tu, Haihan Song, Baohua Qian
Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5(+) CD4(+) T cells, in DLBCL. Data showed that compared to CXCR5(-) CD4(+) T cells, CXCR5(+) CD4(+) T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells...
November 23, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27866903/emerging-concepts-in-t-follicular-helper-cell-responses-to-malaria
#17
REVIEW
Diana S Hansen, Nyamekye Obeng-Adjei, Ann Ly, Lisa J Ioannidis, Peter D Crompton
Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (TFH) cells provide critical help to B cells to generate long-lived antibody responses, they have become the focus of recent studies of Plasmodium-infected mice and humans. The emerging data converge on common themes, namely, that malaria-induced TH1 cytokines are associated with the activation of (i) T-like memory TFH cells with impaired B cell helper function, and (ii) pre-TFH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional TFH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses...
November 17, 2016: International Journal for Parasitology
https://www.readbyqxmd.com/read/27865860/human-regulatory-b-cells-control-tfh-response
#18
Achouak Achour, Quentin Simon, Audrey Mohr, Jean-François Séité, Pierre Youinou, Boutahar Bendaoud, Ibtissem Ghedira, Jacques-Olivier Pers, Christophe Jamin
BACKGROUND: Follicular helper T (Tfh) cells support the terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses but their control of Tfh-dependent humoral immune responses is unknown. OBJECTIVE: To assess the role of Breg cells on Tfh development and function. METHODS: Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate Tfh cells. They were co-cultured with B cells to induce their terminal differentiation...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27863842/development-of-t-follicular-helper-cells-and-their-role-in-disease-and-immune-system
#19
REVIEW
Sadegh Eivazi, Salman Bagheri, Mohammad Sadegh Hashemzadeh, Majdedin Ghalavand, Elmira Safaie Qamsari, Ruhollah Dorostkar, Maryam Yasemi
The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to regulate antibody responses. The production of these cells is associated with the dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers (GC) differentiate into memory and plasma cells (antibody-secreting cells) as humoral responses. In addition, there is strong evidence that TFH cells play a pivotal role in the development of long-lived humoral immunity. Molecular factors such as transcription factors, surface receptors, cytokine and micro RNAs are involved in the formation of TFH cells...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27863820/b-cell-depleting-therapy-regulates-splenic-and-circulating-t-follicular-helper-cells-in-immune-thrombocytopenia
#20
Sylvain Audia, Marzia Rossato, Malika Trad, Maxime Samson, Kim Santegoets, Alexandrine Gautheron, Cornelis Bekker, Olivier Facy, Nicolas Cheynel, Pablo Ortega-Deballon, Mathieu Boulin, Sabine Berthier, Vanessa Leguy-Seguin, Laurent Martin, Marion Ciudad, Nona Janikashvili, Philippe Saas, Timothy Radstake, Bernard Bonnotte
B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet...
November 15, 2016: Journal of Autoimmunity
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