Details

Autor(en) / Beteiligte

• Wu, Hao
• Chen, Yuxin
• Liu, Hong
• Xu, Lin‐Lin
• Teuscher, Paula
• Wang, Shixia
• Lu, Shan
• Dent, Alexander L.

Titel

Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice

Ist Teil von

• European journal of immunology, 2016-05, Vol.46 (5), p.1152-1161

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Follicular helper T (Tfh) cells provide crucial help to germinal center B (GCB) cells for proper antibody production, and a specialized subset of regulatory T cells, follicular regulatory T (Tfr) cells, modulate this process. However, Tfr‐cell function in the GC is not well understood. Here, we define Tfr cells as a CD4+ Foxp3+ CXCR5hi PD‐1hi CD25low TIGIThigh T‐cell population. Furthermore, we have used a novel mouse model (“Bcl6FC”) to delete the Bcl6 gene in Foxp3+ T cells and thus specifically deplete Tfr cells. Following immunization, Bcl6FC mice develop normal Tfh‐ and GCB‐cell populations. However, Bcl6FC mice produce altered antigen‐specific antibody responses, with reduced titers of IgG and significantly increased IgA. Bcl6FC mice also developed IgG antibodies with significantly decreased avidity to antigen in an HIV‐1 gp120 “prime‐boost” vaccine model. In an autoimmune lupus model, we observed strongly elevated anti‐DNA IgA titers in Bcl6FC mice. Additionally, Tfh cells from Bcl6FC mice consistently produce higher levels of Interferon‐γ, IL‐10 and IL‐21. Loss of Tfr cells therefore leads to highly abnormal Tfh‐cell and GCB‐cell responses. Overall, our study has uncovered unique regulatory roles for Tfr cells in the GC response. T‐follicular regulatory (TFR) cells express high levels of the inhibitory receptor TIGIT. TFR cells decrease production of helper cytokines by T‐follicular helper (TFH) cells. TFR cells help shape the antibody response in the germinal center by promoting high affinity IgG and decreasing IgA production.