scholarly journals The Current Researches on T Follicular Helper Cells and Associated Diseases

2012 ◽  
Vol 2 (2) ◽  
pp. 85-91
Author(s):  
Jianwei Zhou ◽  
Cui Kong
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Infectious Diseases ◽  
B Cell ◽  
Humoral Immunity ◽  
Cd4 T Cell ◽  
T Follicular Helper Cells ◽  
Tfh Cells ◽  
Follicular Helper

T follicular helper (Tfh) cell is a new subpopulation of CD4+ T cell family, whose differentiation is affected by Bcl-6, Blimp-1, STAT3, STAT5 and so on, and it could affect or decide the development of other subsets of CD4+ T cells. The important function of Tfh cell is  to help B cell mediate humoral immunity, many researches have proved that Tfh cells participate in the development of autoimmune disease, immunodeficient disease, tumor and    infectious diseases. DOI: http://dx.doi.org/10.3329/jemc.v2i2.12843 J Enam Med Col 2012; 2(2): 85-91

scholarly journals B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells

2011 ◽  
Vol 208 (7) ◽  
pp. 1377-1388 ◽  
Author(s):  
Sau K. Lee ◽  
Robert J. Rigby ◽  
Dimitra Zotos ◽  
Louis M. Tsai ◽  
Shimpei Kawamoto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Antibody Responses ◽  
B Cell Differentiation ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Microbial Infections

T follicular helper cells (Tfh cells) localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell–expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6+ T cells appear at the T–B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6+ PD-1hi T cells, which are found within the GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl-6+ T cells are necessary at B cell priming to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells.

scholarly journals Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells

2011 ◽  
Vol 208 (5) ◽  
pp. 987-999 ◽  
Author(s):  
Laura M. Fahey ◽  
Elizabeth B. Wilson ◽  
Heidi Elsaesser ◽  
Chris D. Fistonich ◽  
Dorian B. McGavern ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infection ◽  
Cd4 T Cells ◽  
Viral Infections ◽  
Viral Persistence ◽  
Cd4 T Cell ◽  
T Follicular Helper Cells ◽  
Helper Cells ◽  
Follicular Helper

CD4 T cell responses are crucial to prevent and control viral infection; however, virus-specific CD4 T cell activity is considered to be rapidly lost during many persistent viral infections. This is largely caused by the fact that during viral persistence CD4 T cells do not produce the classical Th1 cytokines associated with control of acute viral infections. Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control of persistent viral replication. We now demonstrate that CD4 T cell function is not extinguished as a result of viral persistence. Instead, viral persistence and prolonged T cell receptor stimulation progressively redirects CD4 T cell development away from the Th1 response induced during an acute infection toward T follicular helper cells. Importantly, this sustained CD4 T cell functionality is critical to maintain immunity and ultimately aid in the control of persistent viral infection.

scholarly journals Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses

2020 ◽  
Author(s):  
Can Cui ◽  
Jiawei Wang ◽  
Ping-Min Chen ◽  
Kelli A. Connolly ◽  
Martina Damo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Interactions ◽  
Tumor Control ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper ◽  
T Follicular Helper Cell

AbstractCD4+ T follicular helper (TFH) cells provide help to B cells, which is critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found TFH cells correlated with GC B cells and with prolonged survival of lung adenocarcinoma (LUAD) patients. To investigate further, we developed an LUAD model, in which tumor cells expressed B-cell- and T-cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells were necessary for tumor control, as were effector CD8+ T cells. The latter were reduced in the absence of T cell-B cell interactions or the IL-21 receptor. IL-21 was produced primarily by TFH cells, development of which required B cells. Moreover, development of tumor-specific TFH cell-responses was also reliant upon tumors that expressed B-cell-recognized neoantigens. Thus, tumor-neoantigens themselves can control the fate decisions of tumor-specific CD4+ T cells by facilitating interactions with tumor-specific B cells.Abstract Figure

scholarly journals IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells

2010 ◽  
Vol 207 (13) ◽  
pp. 2895-2906 ◽  
Author(s):  
Marcel Batten ◽  
Nandhini Ramamoorthi ◽  
Noelyn M. Kljavin ◽  
Cindy S. Ma ◽  
Jennifer H. Cox ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Germinal Center ◽  
Dependent Manner ◽  
High Affinity ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Cell Clones

Maturation and selection of high-affinity B cell clones in the germinal center (GC) relies on support from T follicular helper (TFH) cells. TFH cells are characterized by their localization to the B cell follicle and their high expression of the costimulatory molecules ICOS and PD1 and the cytokine IL-21, which promotes immunoglobulin (Ig) class switching and production by B cells. We show that the heterodimeric cytokine IL-27 is critical for the function of TFH cells and for normal and pathogenic GC responses. IL-27 signaling to T cells results in the production of IL-21, a known autocrine factor for the maintenance of TFH cells, in a STAT3-dependent manner. IL-27 also enhances the survival of activated CD4+ T cells and the expression of TFH cell phenotypic markers. In vivo, expression of the IL-27Rα chain is required to support IL-21 production and TFH cell survival in a T cell–intrinsic manner. The production of high-affinity antibodies is reduced, and pristane-elicited autoantibodies and glomerulonephritis are significantly diminished, in Il27ra−/− mice. Together, our data show a nonredundant role for IL-27 in the development of T cell–dependent antibody responses.

scholarly journals Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production

2012 ◽  
Vol 210 (1) ◽  
pp. 143-156 ◽  
Author(s):  
Matthieu Perreau ◽  
Anne-Laure Savoye ◽  
Elisa De Crignis ◽  
Jean-Marc Corpataux ◽  
Rafael Cubas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Productive Infection ◽  
Cell Populations ◽  
Cell Compartment ◽  
Tfh Cells ◽  
Follicular Helper

In the present study, we have investigated the distribution of HIV-specific and HIV-infected CD4 T cells within different populations of memory CD4 T cells isolated from lymph nodes of viremic HIV-infected subjects. Four memory CD4 T cell populations were identified on the basis of the expression of CXCR5, PD-1, and Bcl-6: CXCR5−PD-1−Bcl-6−, CXCR5+PD-1−Bcl-6−, CXCR5−PD-1+Bcl-6−, and CXCR5+PD-1+Bcl-6+. On the basis of Bcl-6 expression and functional properties (IL-21 production and B cell help), the CXCR5+PD-1+Bcl-6+ cell population was considered to correspond to the T follicular helper (Tfh) cell population. We show that Tfh and CXCR5−PD-1+ cell populations are enriched in HIV-specific CD4 T cells, and these populations are significantly increased in viremic HIV-infected subjects as compared with healthy subjects. The Tfh cell population contained the highest percentage of CD4 T cells harboring HIV DNA and was the most efficient in supporting productive infection in vitro. Replication competent HIV was also readily isolated from Tfh cells in subjects with nonprogressive infection and low viremia (<1,000 HIV RNA copies). However, only the percentage of Tfh cells correlated with the levels of plasma viremia. These results demonstrate that Tfh cells serve as the major CD4 T cell compartment for HIV infection, replication, and production.

scholarly journals Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

2021 ◽  
Author(s):  
Suhas Sureshchandra ◽  
Sloan A. Lewis ◽  
Brianna Doratt ◽  
Allen Jankeel ◽  
Izabela Ibraim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Single Cell ◽  
Cd8 T Cells ◽  
Natural Infection ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Responses

mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used single-cell RNA sequencing and functional assays to compare humoral and cellular responses to two doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4 T cells, and robust antigen-specific polyfunctional CD4 T cell responses in all vaccinees. On the other hand, CD8 T cell responses were both weak and variable. Interestingly, clonally expanded CD8 T cells were observed in every vaccinee, as observed following natural infection. TCR gene usage, however, was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of larger CD8 T cell clones occupied distinct clusters, likely due to the recognition of a broader set of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response where early CD4 T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8 T cells, together capable of contributing to future recall responses.

scholarly journals Induction of human IgE synthesis by CD4+ T cell clones. Requirement for interleukin 4 and low molecular weight B cell growth factor.

1989 ◽  
Vol 170 (5) ◽  
pp. 1477-1493 ◽  
Author(s):  
R H DeKruyff ◽  
T Turner ◽  
J S Abrams ◽  
M A Palladino ◽  
D T Umetsu
Keyword(s):  
Molecular Weight ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cell ◽  
Low Molecular Weight ◽  
Cell Clones ◽  
B Cell Growth Factor ◽  
Ige Synthesis

We have analyzed in detail the precise requirements for the induction of human IgE synthesis using several experimental approaches with purified B cells and well-characterized alloantigen-specific CD4+ T cell clones expressing different profiles of lymphokine secretion. Using these clones under cognate conditions in which the B cells expressed alloantigens recognized by the cloned T cells, we have confirmed that IL-4 is required for the induction of IgE synthesis, but we have clearly demonstrated that IL-4 by itself is not sufficient. With several cloned CD4+ T cell lines, including an IL-4-producing clone that could not induce IgE synthesis, and cloned T cells pretreated with cyclosporin A to inhibit lymphokine synthesis, we showed that Th cell-B cell interactions are necessary for IgE synthesis, and that low molecular weight B cell growth factor (LMW-BCGF) and IL-4, in combination, are lymphokines of major importance in the induction of IgE synthesis. Together our results indicate that optimal induction of an IgE-specific response requires the exposure of B cells to a particular complex of signals that include (a) a signal(s) involving Th-B cell interaction that primes B cells to receive additional signals from soluble lymphokines, (b) a specific B cell proliferative signal provided by LMW-BCGF, and (c) a specific B cell differentiation signal provided by IL-4.

scholarly journals X4-Tropic Latent HIV-1 Is Enriched in Peripheral Follicular Helper T Cells and Is Correlated with Disease Progression

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Fei Yu ◽  
Qijuan Li ◽  
Xi Chen ◽  
Jun Liu ◽  
Linghua Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
Clinical Relevance ◽  
Cell Recovery ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Cell Counts ◽  
Latent Hiv ◽  
Hiv 1

ABSTRACT Follicular helper T (TFH) cells have been shown to support productive human immunodeficiency virus type 1 (HIV-1) replication and to serve as a key component of the latent viral reservoir. However, the viral characteristics of this latent reservoir and the clinical relevance of this reservoir remain unclear. In this study, we assessed the tropic composition of latent viruses from peripheral TFH (pTFH), non-TFH memory, and naive CD4+ T cells from individuals with HIV-1 infections on suppressive combined antiretroviral therapy (cART). X4-tropic latent HIV-1 was preferentially enriched in pTFH cells compared to levels in the other two subsets. Interestingly, the ratio of X4-tropic latent HIV-1 in pTFH cells not only was robustly and inversely correlated with blood CD4+ T cell counts across patients but also was prognostic of CD4+ T cell recovery in individuals on long-term cART. Moreover, patients with higher X4-tropic latent HIV-1 ratios in pTFH cells showed greater risks of opportunistic coinfections. These findings reveal the characteristics of latent HIV-1 in TFH cells and suggest that the ratio of X4-tropic latent HIV-1 in pTFH cells is a valuable indicator for disease progression and cART efficacy. IMPORTANCE TFH cells have been shown to harbor a significant amount of latent HIV-1; however, the viral characteristics of this reservoir and its clinical relevance remain largely unknown. In this study, we demonstrate that X4-tropic latent HIV-1 is preferentially enriched in pTFH cells, which also accurately reflects the viral tropism shift. The ratio of X4-tropic proviruses in pTFH cells but not in other memory CD4+ T cell subsets is inversely and closely correlated with blood CD4+ T cell counts and CD4+ T cell recovery rates with cART. Our data suggest that the ratio of X4-tropic provirus in peripheral TFH cells can be easily measured and reflects disease progression and treatment outcomes during cART.

A Variety of T-Cell Subsets Contribute to CD4+ T-Cell Infiltration in Diffuse Large B-Cell Lymphoma and Both Total CD4+ and CD4+FoxP3+ T-Cell Numbers Predict Clinical Outcome,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3684-3684
Author(s):  
Matthew J Ahearne ◽  
Kaljit S Bhuller ◽  
Roger Hew ◽  
Giovanna Roncador ◽  
Martin J.S. Dyer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Outcome ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
Good Clinical Outcome ◽  
Logrank Test ◽  
Tfh Cells

Abstract Abstract 3684 CD4+ T-cells can be distinguished into subsets on the basis of surface marker expression and growth factor production. Follicular helper T-cells (Tfh cells) are characterized by the co-expression of surface markers (CD4, ICOS, PD1 and CXCR5) and nuclear BCL6. Normal germinal centre formation requires Tfh cells but is repressed by another CD4+ T-cell subset, Tregs, (demonstrating CD4 and CD25 expression with nuclear FoxP3). The numbers and architecture of infiltrating T-cells predict clinical outcome in follicular lymphoma but although T-cells are a component of diffuse large B cell lymphoma (DLBCL), the relative numbers of CD4+ T-cells and their Tfh and Treg subsets or their association with clinical outcome is not known. We used immunohistochemistry to investigate infiltration by total CD4+, Treg and Tfh cells in cases (n=23) from one centre. The male:female was 1.3:1.0, the age range was 30 to 78 years (median 65 years) and the anticipated association between overall survival and LDH (logrank test, P=0.02) was observed. Patients were treated with R-CHOP with a 21-day cycle. Histological sections were stained with anti-CD4, anti-PD1 and anti-FoxP3 antibodies. For each antibody the area of staining was measured using ImageJ software from 10 high power fields from the same area of each histological section. Tfh cells were identified by strong surface expression of PD1 and Tregs by nuclear expression of FoxP3. CD4+ T-cell infiltration varied by ∼50-fold, and could be diffuse or focal. In 13 cases (57%) the majority of CD4+ T-cells were neither FoxP3+ nor PD1+. Total CD4+ T-cell numbers were positively correlated with FoxP3 (P=0.04) (Figure 1) and with PD1 (P=0.009) (Figure 2) expressing cells suggesting that these subsets were expanded as part of a reaction to the lymphoma capable of stimulating several CD4+ T-cell subsets. High CD4+ (Figure 3) and PD1+ staining predicted good clinical outcome (logrank test, P=0.08) with median survival not being reached at 5 years, but the amount of FoxP3+ staining appeared to be a superior prognostic marker (logrank test, P=0.0069) (Figure 4). There was no association between the cell of origin classification of DLBCL (GCB or ABC) as defined immunohistochemically, and CD4, FoxP3 or PD1 expression. In summary, we have shown that numbers of infiltrating CD4+ T-cells vary between cases of DLBCL and comprises several T-cell subsets including Treg and Tfh cells. No consensus has been reached on the clinical significance of FoxP3+ cell infiltration in DLBCL. Whilst some workers have shown FoxP3 to be associated with a good clinical outcome (Tzankov A., et al. 2008; Lee N., et al. 2008), others have not found a relationship to prognosis (Hasselblom S. et al., 2007). Our data shows that the FoxP3+ Treg cell subset is associated with good clinical outcome but surprisingly we found that both increased total CD4+ T-cells and PD1+ Tfh cells also carry a good prognosis. Disclosures: Wagner: Roche: Honoraria.

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