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Follicular t helper cell

Elizabeth F Wallin, Danika L Hill, Michelle A Linterman, Kathryn J Wood
Background: T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells via the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients. Methods: Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation...
2018: Frontiers in Immunology
Satoshi Arai, Noriyuki Iwabuchi, Sachiko Takahashi, Jin-Zhong Xiao, Fumiaki Abe, Satoshi Hachimura
Antigen-specific immunoglobulin (Ig) A plays a major role in host defense against infections in gut mucosal tissue. Follicular helper T (Tfh) cells are located in germinal centers and promote IgA production via interactions with germinal center B cells. Several studies have demonstrated that some lactic acid bacteria (LAB) strains activate the host's acquired immune system, inducing IgA secretion in the intestine. However, the precise molecular mechanisms underlying the effects of LAB on IgA production and Tfh cells are not fully resolved...
2018: PloS One
Vanesa Cunill, Margarita Massot, Antonio Clemente, Carmen Calles, Valero Andreu, Vanessa Núñez, Antonio López-Gómez, Rosa María Díaz, María de Los Reyes Jiménez, Jaime Pons, Cristòfol Vives-Bauzà, Joana Maria Ferrer
Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, although several evidences also demonstrate a B cell involvement in its etiology. Follicular T helper (Tfh) cells, a CXCR5-expressing CD4+ T cell subpopulation, are essential in the regulation of B cell differentiation and maintenance of humoral immunity. Alterations in circulating (c)Tfh distribution and/or function have been associated with autoimmune diseases including MS. Dimethyl fumarate (DMF) is a recently approved first-line treatment for relapsing-remitting MS (RRMS) patients whose mechanism of action is not completely understood...
2018: Frontiers in Immunology
Roberta Zappasodi, Sadna Budhu, Matthew D Hellmann, Michael A Postow, Yasin Senbabaoglu, Sasikanth Manne, Billel Gasmi, Cailian Liu, Hong Zhong, Yanyun Li, Alexander C Huang, Daniel Hirschhorn-Cymerman, Katherine S Panageas, E John Wherry, Taha Merghoub, Jedd D Wolchok
A significant proportion of cancer patients do not respond to immune checkpoint blockade. To better understand the molecular mechanisms underlying these treatments, we explored the role of CD4+ Foxp3- T cells expressing PD-1 (4PD1hi ) and observed that 4PD1hi accumulate intratumorally as a function of tumor burden. Interestingly, CTLA-4 blockade promotes intratumoral and peripheral 4PD1hi increases in a dose-dependent manner, while combination with PD-1 blockade mitigates this effect and improves anti-tumor activity...
June 11, 2018: Cancer Cell
Erxia Shen, Qin Wang, Hardis Rabe, Wenquan Liu, Harvey Cantor, Jianmei W Leavenworth
Lineage commitment and differentiation into CD4+ T cell subsets reflect an interplay between chromatin regulators and transcription factors (TF). Follicular T cell development is regulated by the Bcl6 TF, which helps determine the phenotype and follicular localization of both CD4+ follicular helper T cells (TFH ) and follicular regulatory T cells (TFR ). Here we show that Bcl6-dependent control of follicular T cells is mediated by a complex formed between Bcl6 and the Mi-2β-nucleosome-remodeling deacetylase complex (Mi-2β-NuRD)...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
J Magarian Blander, Gaetan Barbet
Live attenuated vaccines elicit stronger protective immunity than dead vaccines. Distinct PAMPs designated as vita-PAMPs signify microbial viability to innate immune cells. Two vita-PAMPs have been characterized: cyclic-di-adenosine-monophosphate (c-di-AMP) and prokaryotic messenger RNA (mRNA). c-di-AMP produced by live Gram-positive bacteria elicits augmented production of STING-dependent type-I interferon, whereas prokaryotic mRNA from live bacteria is detected by TLR8 enabling discrimination of live from dead bacteria...
June 8, 2018: Current Opinion in Pharmacology
Ute Greczmiel, Annette Oxenius
Chronic infections with non-cytopathic viruses constitutively expose virus-specific adaptive immune cells to cognate antigen, requiring their numeric and functional adaptation. Virus-specific CD8 T cells are compromised by various means in their effector functions, collectively termed T cell exhaustion. Alike CD8 T cells, virus-specific CD4 Th1 cell responses are gradually downregulated but instead, follicular T helper (TFH ) cell differentiation and maintenance is strongly promoted during chronic infection...
2018: Frontiers in Immunology
Marco Puthenparampil, Antonio Zito, Giorgia Pantano, Lisa Federle, Erica Stropparo, Silvia Miante, Giustina De Silvestro, Mario Plebani, Paolo Gallo
BACKGROUND: Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell. OBJECTIVE: To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. METHODS: Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis...
June 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Karl A Brokstad, Marita Fredriksen, Fan Zhou, Brith Bergum, Johan G Brun, Rebecca J Cox, Kathrine Skarstein
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by exocrine gland dysfunction, mainly causing sicca symptoms. B cells have a prominent role in SS, and the T follicular helper (TFH ) cells provide B cells with survival- and specialization signals in germinal centers. Here we investigate peripheral TFH cells in pSS. Sixteen pSS patients and healthy controls were enrolled in the study, with thirteen women and three men in each group. Whole blood was collected and separated into PBMC and plasma, followed by cryopreservation...
June 8, 2018: Scandinavian Journal of Immunology
Monica Centa, Kajsa E Prokopec, Manasa G Garimella, Katrin Habir, Lisa Hofste, Julian M Stark, Albert Dahdah, Chris A Tibbit, Konstantinos A Polyzos, Anton Gisterå, Daniel K Johansson, Nobuyo N Maeda, Göran K Hansson, Daniel F J Ketelhuth, Jonathan M Coquet, Christoph J Binder, Mikael C I Karlsson, Stephen Malin
OBJECTIVE: Dyslipidemia is a component of the metabolic syndrome, an established risk factor for atherosclerotic cardiovascular disease, and is also observed in various autoimmune and chronic inflammatory conditions. However, there are limited opportunities to study the impact of acquired dyslipidemia on cardiovascular and immune pathology. APPROACH AND RESULTS: We designed a model system that allows for the conversion to a state of acute hyperlipidemia in adult life, so that the consequences of such a transition could be observed, through conditionally deleting APOE (apolipoprotein E) in the adult mouse...
June 7, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Kenta Iwasaki, Nana Kitahata, Takahisa Hiramitsu, Takayuki Yamamoto, Takayuki Noda, Manabu Okada, Shunji Narumi, Yoshihiko Watarai, Yuko Miwa, Kazuharu Uchida, Matsuoka Yutaka, Kosei Horimi, Takaaki Kobayashi
It is unclear to what extent follicular helper T-cell (Tfh) development and de novo donor specific HLA antibody (DSA) production could be influenced by immunosuppressive agents, particularly calcineurin inhibitor (CNI), after kidney transplantation. Here, the effects of immunosuppressive agents on Tfh-mediated B-cell activation and antibody production were investigated. In vitro circulating Tfh (cTfh; memory CD4+CXCR5+)/B-cell (CD19+) co-culture assays revealed that CNI considerably inhibited cTfh-mediated B-cell activation and IgG antibody secretion through the suppression of IL-21 and IL-2...
June 7, 2018: International Immunology
Koichi Ohshima, Hiroaki Miyoshi, Kyohei Yamada
Angioimmunoblastic T-cell lymphoma (AITL) originates from follicular helper T cells and shows variable biological and clinical presentations. The survival rate of patients with AITL did not correlate with T-cell clonality, the presence of EBV-infected cells, EBV-DNA copy number, or IgH rearrangements. However, tumor-associated macrophage/M2 macrophages significantly correlated with worse overall survival (OS). Additionally, patients with composite lymphoma with diffuse large B cell lymphoma and AITL showed worse OS...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Yoshihiro Inamoto
Chronic graft-versus-host disease (cGVHD) occurs in approximately 40% of patients who undergo allogeneic hematopoietic cell transplantation. It affects various organs and causes significant morbidity and mortality. The manifestations of cGVHD resemble those of autoimmune diseases. Inflammation, cellular immunity, humoral immunity, and fibrosis are implicated in cGVHD pathogenesis. The 2005 NIH consensus criteria for cGVHD have set standards for designing and reporting clinical trials, and the criteria were revised in 2014 to incorporate accumulated evidence and questions...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Qingyan Lu, Xuan Luo, Chaoming Mao, Tingting Zheng, Baocui Liu, Xin Dong, Yuepeng Zhou, Chengcheng Xu, Xiao Mou, Fei Wu, Ling Bu, Guoyue Yuan
Hashimoto's thyroiditis (HT) is considered a T helper-type 1 (Th1) cytokine-dominant autoimmune thyroid disease. Caveolin-1 (Cav-1), a part of the thyroxisome multiprotein complex, is localized at the apical pole of thyrocytes and is indispensable for synthesis of thyroid hormones and modulation of oxidative stress in order to avoid cell damage and apoptosis. Reduced autophagy induces thyroid follicular cells (TFC) apoptosis by activating reactive oxygen species (ROS) in HT patients. Nevertheless, whether Cav-1 has roles in the regulation of autophagy remains largely unclear...
June 6, 2018: Endocrine Journal
Ruihua Li, Ju Liu, Shipo Wu, Xiaodong Zai, Yaohui Li, Qiaoling Yang, Lihua Hou, Junjie Xu, Wei Chen
Adenoviral vectors (AdV) are considered promising candidates for vaccine applications. A prominent group of toll-like receptors (TLRs) participate in the Adenovirus (Ad)-induced adaptive immune response, yet there is little information regarding the role of TLR4 in AdV-induced immune responses in recent literature. We investigated the function of TLR4 in both adaptive and innate immune responses to an AdV-based anthrax vaccine. By immunizing wild-type and TLR4 knockout (TLR4-KO) mice, we revealed the requirement of TLR4 in AdV-induced innate responses...
June 7, 2018: Immunology
Yaxing Hao, Yifei Wang, Xiaobing Liu, Xia Yang, Pengcheng Wang, Qin Tian, Qiang Bai, Xiangyu Chen, Zhirong Li, Jialin Wu, Zhunyi Xie, Xinyuan Zhou, Yuyang Zhou, Zhinan Yin, Yuzhang Wu, Lilin Ye
Follicular helper CD4+ T (TFH ) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of TFH cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate TFH differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infection, we demonstrate that mTOR complex 2 (mTORC2) kinase integrates TCR signaling and ICOS-mediated co-stimulation to promote late differentiation and functional maturation of virus-specific TFH cells...
2018: Frontiers in Immunology
Minglu Xiao, Xiangyu Chen, Ran He, Lilin Ye
The combination antiretroviral therapeutic (cART) regime effectively suppresses human immunodeficiency virus (HIV) replication and prevents progression to acquired immunodeficiency diseases. However, cART is not a cure, and viral rebound will occur immediately after treatment is interrupted largely due to the long-term presence of an HIV reservoir that is composed of latently infected target cells that maintain a quiescent state or persistently produce infectious viruses. CD4 T cells that reside in B-cell follicles within lymphoid tissues, called follicular helper T cells (TFH), have been identified as a major HIV reservoir...
2018: Frontiers in Immunology
Zhanshan Cha, Haihui Gu, Yan Zang, Zi Wang, Jinqi Li, Weihua Huang, Aihua Qin, Lishuang Zhu, Xiaohua Tu, Ning Cheng, Haihan Song, Baohua Qian
CD4+ CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells possess critical roles in suppressing the germinal center reaction, B cell activation, and follicular helper T cell (Tfh) cytokine secretion. Since diffuse large B cell lymphoma (DLBCL) can arise from B cells undergoing germinal center reaction and/or differentiation, we hypothesized that Tfr cells might be involved in DLBCL. In the present study, we recruited thirty-five DLBCL patients and twenty-five healthy controls. Data showed that DLBCL patients presented an enrichment of circulating CD4+ CXCR5+ Foxp3+ Tfr cells compared to controls...
June 1, 2018: International Immunopharmacology
Takayuki Katsuyama, George C Tsokos, Vaishali R Moulton
Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to "self" leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites...
2018: Frontiers in Immunology
Jun Guo, Cong Zhao, Fang Wu, Liang Tao, Chunmei Zhang, Daidi Zhao, Shuya Yang, Dongbo Jiang, Jing Wang, Yuanjie Sun, Zhuyi Li, Hongzeng Li, Kun Yang
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have been proved to be T cell-mediated autoimmune diseases. Recent researches indicate that humoral immunity is also involved in the pathogenesis of these disorders. T follicular helper (Tfh) cells are critical for B cell differentiation and antibody production. However, the role of Tfh cells in MS and EAE remains unclear. Here, we found elevated frequencies of CD4+ CXCR5+ PD-1+ Tfh-like cells in both MS patients and EAE. In EAE mice, Tfh-like cells, together with B cells, were found in the ectopic lymphoid structures in spinal cords...
2018: Frontiers in Immunology
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