Insights into the development and regulation of T follicular helper cells

Wali, Shradha; Sahoo, Anupama; Puri, Sushant; Alekseev, Andrei; Nurieva, Roza

doi:10.1016/j.cyto.2016.06.010

Cited by 13 publications

(21 citation statements)

References 139 publications

(243 reference statements)

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“…3 The differentiation of naive CD4 + T cells toward Tfh cells is a multistep programme in which cell-to-cell contacts as well as cytokine environment are critical. 4,5 Mature antigen-presenting cells migrate from the periphery to the lymphoid tissues to activate their cognate naive CD4 + T cells in the T-cell zone. Upon activation, CD4 + T cells up-regulate CXCR5 and migrate to the B-cell zone where they will encounter cognate B cells.…”

Section: Discussionmentioning

confidence: 99%

“…Several cytokines, such as interleukin-6 (IL-6), IL-21 and IL-12 have been involved in the development of Tfh cells. 4,6 After considering the recent data on Tfh cell dynamics in HIV/simian immunodeficiency virus (SIV)…”

Section: Discussionmentioning

confidence: 99%

“…B‐cell maturation and differentiation toward memory and plasma cells is dependent on a subset of CD4 + T cells that express CXCR5 and migrate to B‐cell follicles, namely T follicular helper (Tfh) cells . The differentiation of naive CD4 + T cells toward Tfh cells is a multistep programme in which cell‐to‐cell contacts as well as cytokine environment are critical . Mature antigen‐presenting cells migrate from the periphery to the lymphoid tissues to activate their cognate naive CD4 + T cells in the T‐cell zone.…”

mentioning

confidence: 99%

“…The T‐cell–B‐cell interactions through surface proteins provide further signals allowing pre‐Tfh cells to enter the B‐cell follicles and facilitate the germinal center (GC) reaction. Several cytokines, such as interleukin‐6 (IL‐6), IL‐21 and IL‐12 have been involved in the development of Tfh cells …”

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confidence: 99%

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From dendritic cells to B cells dysfunctions during HIV‐1 infection: T follicular helper cells at the crossroads

2017

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Summary T follicular helper (Tfh) cells are essential for B‐cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal centre, where they are the main source of replicative HIV‐1 and represent a major reservoir. Paradoxically, Tfh cell numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV‐1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure. The purpose of this review is to summarize the recent advance in our understanding of Tfh cell dynamics during HIV/SIV infection. In particular, to explore the possible causes of their expansion in lymphoid tissues by discussing the impact of HIV‐1 infection on dendritic cells, to identify the molecular players rendering Tfh cells highly susceptible to HIV‐1 infection, and to consider the contribution of regulatory follicular T cells in shaping Tfh cell functions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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From dendritic cells to B cells dysfunctions during HIV‐1 infection: T follicular helper cells at the crossroads

2017

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“…T fh cells synthesize characteristic cytokines (such as interleukin [IL]-21 and IL-4) that facilitate antibody production by and class-switch recombination events in B-cells. Over recent years, it has been shown that the expression of typical transcription factors (such as Bcl-6 and c-MAF)along with their mutual regulationis of crucial significance for the initial differentiation of, and essential functions thereafter, of T fh cells (Crotty 2014;Qi et al 2014;Butler and Kulu 2015;Jogdand et al 2016;Wali et al 2016;Qin et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Di-(2-ethylhexyl)-phthalate interferes with T-follicular helper cell differentiation and cytokine secretion through signaling lymphocytic activation molecule family member-1

Han

Wang

Pang

et al. 2019

Journal of Immunotoxicology

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2019) Di-(2-ethylhexyl)-phthalate interferes with T-follicular helper cell differentiation and cytokine secretion through signaling lymphocytic activation molecule family member-ABSTRACT Exposure to the widely-used phthalate plasticizer di-(2-ethylhexyl)-phthalate (DEHP) has been shown to be closely related to an increased prevalence of allergic diseases in infants and juveniles. Earlier work in our laboratory found that DEHP-related anaphylactic responses could be ascribed to T-follicular helper (T fh ) cell hyperfunction directly. The T fh cell, a newly identified CD4 þ T H cell subset, until recently has been considered as a key player in humoral immunity. T fh cells can respond to stimulation through various receptors. Signaling lymphocytic activation molecule family member-1 (SLAMF1, CD150) is a surface co-stimulatory receptor that can bind to an intracytoplasmic adaptor signaling lymphocytic activation molecule-associated protein (SAP) to initiate downstream signaling cascades, regulating some events of immune response. The present study explored the role of SLAMF1 in T fh cell differentiation and cytokine secretion under the condition of DEHP exposure. Using a weanling mice model of DEHP gavage with ovalbumin (OVA) sensitization, it was found that DEHP acted as an immunoadjuvant to elevate SLAMF1 and SAP expression in host T fh cells. Ex vivo studies of effects from DEHP exposure on T fh cells from OVAsensitized hosts showed that DEHP acted in an adjuvant-like manner to promote the expression of adaptor protein SAP, transcription factors Bcl-6 and c-MAF, and cytokines interleukin (IL)-21 and IL-4 in T fh cells. Transfection of these T fh cells with Slamf1 small interfering RNA prior to exposure to the DEHP attenuated the over-expression of these molecules that was caused by the DEHP. In conclusion, this study demonstrated that DEHP, via a SLAMF1-mediated pathway, can impact on T fh cell differentiation and their ability to form select cytokines. ARTICLE HISTORY

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Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4‐Related Disease

Chen

Lin

Yang

et al. 2018

Arthritis & Rheumatology

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ObjectiveTo determine the number and function of follicular helper T (Tfh) cell subsets in IgG4‐related disease (IgG4‐RD).MethodsMononuclear cells from the peripheral blood and involved tissue of patients with IgG4‐RD were assessed for Tfh cells and their subsets, and levels of B cell lymphoma 6 (Bcl‐6), B lymphocyte–induced maturation protein 1 (BLIMP‐1), and interleukin‐21 (IL‐21) messenger RNA (mRNA). Immunohistochemical and immunofluorescence techniques were used to assess the involved tissue of patients to determine the location of IL‐21, Bcl‐6, and CD4+CXCR5+ Tfh cells. Furthermore, the ability of circulating Tfh (cTfh) cell subsets to induce B cell proliferation, apoptosis, and differentiation and to produce IgG4 was explored in cell cocultures in vitro.ResultsFrequencies of cTfh cells were significantly increased in the peripheral blood of patients with IgG4‐RD, and even higher frequencies were observed in the involved tissue. Percentages of programmed cell death protein 1 in CD4+CXCR5+ICOS+ cTfh cells were positively correlated with the serum levels of IgG and IgG4, IgG4:IgG ratio, number of involved organs, and frequency of CD19+CD24−CD38high plasmablasts/plasma cells. Levels of BLIMP‐1 and IL‐21 mRNA in peripheral CD4+ T cells were increased in patients with IgG4‐RD compared to healthy controls, and this was correlated with the levels of serum IgG4. Moreover, in the involved tissue, Bcl‐6, IL‐21, and Tfh cells were highly expressed. Compared to cTfh cells from healthy controls, cTfh cells from patients with IgG4‐RD could facilitate B cell proliferation and inhibit B cell apoptosis more efficiently, and enhanced the differentiation of naive B cells into switched memory B cells and plasmablasts/plasma cells, with a resultant increase in the secretion of IgG4. Notably, the cTfh1 and cTfh2 cell subsets were the most effective at providing B cell help.ConclusionTfh cell subsets are expanded in IgG4‐RD and may play pivotal roles in the pathogenesis of the disease.

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Insights into the development and regulation of T follicular helper cells

Cited by 13 publications

References 139 publications

From dendritic cells to B cells dysfunctions during HIV‐1 infection: T follicular helper cells at the crossroads

From dendritic cells to B cells dysfunctions during HIV‐1 infection: T follicular helper cells at the crossroads

Di-(2-ethylhexyl)-phthalate interferes with T-follicular helper cell differentiation and cytokine secretion through signaling lymphocytic activation molecule family member-1

Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4‐Related Disease

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