scholarly journals Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression

2014 ◽  
Vol 211 (3) ◽  
pp. 545-561 ◽  
Author(s):  
Martin Vaeth ◽  
Gerd Müller ◽  
Dennis Stauss ◽  
Lena Dietz ◽  
Stefan Klein-Hessling ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Germinal Center ◽  
Helper T Cells ◽  
Germinal Center Reaction ◽  
High Affinity ◽  
Follicular Helper ◽  
Physiological Relevance ◽  
Humoral Autoimmunity ◽  
Cxcr5 Expression

Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4+CXCR5+ follicular helper T cells (TFH) and inhibited by CD4+CXCR5+Foxp3+ follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells.

Reduced germinal center follicular helper T cells but normal follicular regulatory T cells in the tonsils of a patient with a mutation in the PI3KR1 gene

2016 ◽  
Vol 164 ◽  
pp. 43-44 ◽  
Author(s):  
Roberta Di Fonte ◽  
Manuela Baronio ◽  
Alessandro Plebani ◽  
Vassilios Lougaris ◽  
Georgia Fousteri
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Germinal Center ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Follicular Helper

scholarly journals Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2795-2810 ◽  
Author(s):  
Masashi Watanabe ◽  
Chiharu Fujihara ◽  
Andrea J. Radtke ◽  
Y. Jeffrey Chiang ◽  
Sumeena Bhatia ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Germinal Center ◽  
Helper T Cells ◽  
Vaccine Responses ◽  
High Affinity ◽  
Prevailing Paradigm ◽  
Follicular Helper ◽  
Cd40 Expression ◽  
Antigen Presenting

T cell–dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity.

scholarly journals PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e99127 ◽  
Author(s):  
Hong-Jai Park ◽  
Do-Hyun Kim ◽  
Jin-Young Choi ◽  
Won-Ju Kim ◽  
Ji Yun Kim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Germinal Center ◽  
Cell Activation ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Follicular Helper ◽  
Germinal Center Formation

scholarly journals CD10 delineates a subset of human IL-4 producing follicular helper T cells involved in the survival of follicular lymphoma B cells

Blood ◽  
2015 ◽  
Vol 125 (15) ◽  
pp. 2381-2385 ◽  
Author(s):  
Patricia Amé-Thomas ◽  
Sylvia Hoeller ◽  
Catherine Artchounin ◽  
Jan Misiak ◽  
Mounia Sabrina Braza ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Germinal Center ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Follicular Helper ◽  
Key Points ◽  
Cell Niche

Key Points CD10 identifies a unique subset of fully functional germinal center TFH that are activated and amplified within the FL cell niche. FL CD10pos TFH specifically display an IL-4hiIFN-γlo cytokine profile and encompass the malignant B-cell-supportive TFH subset.

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