CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance

被引：64

作者：

Chen, Yuhong ^{[1
]}

Yu, Mei ^{[1
]}

Zheng, Yongwei ^{[1
]}

Fu, Guoping ^{[1
]}

Xin, Gang ^{[1
]}

Zhu, Wen ^{[1
,2
]}

Luo, Lan ^{[1
,3
]}

Burns, Robert ^{[1
]}

Li, Quan-Zhen ^{[4
]}

Dent, Alexander L. ^{[5
]}

Zhu, Nan ^{[1
]}

Cui, Weiguo ^{[1
]}

Malherbe, Laurent ^{[6
]}

Wen, Renren ^{[1
]}

Wang, Demin ^{[1
,2
,7
]}

机构：

[1] Versiti, Blood Res Inst, Milwaukee, WI 53233 USA

[2] Med Coll Wisconsin, Dept Microbiol & Immunol, Milwaukee, WI 53226 USA

[3] Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China

[4] Univ Texas Southwestern Med Ctr Dallas, Dept Immunol & Internal Med, Dallas, TX 75390 USA

[5] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA

[6] Eli Lilly, Toxicol Div, Indianapolis, IN USA

[7] Fujian Normal Univ, Coll Life Sci, Biomed Res Ctr South China, Fuzhou, Fujian, Peoples R China

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷

关键词：

VIVO CD40-GP39 INTERACTIONS; DEPENDENT HUMORAL IMMUNITY; CXC CHEMOKINE RECEPTOR-5; NEGATIVE SELECTION; MESSENGER-RNAS; NKT CELLS; EXPRESSION; DIFFERENTIATION; ANTIBODY; ANTIGEN;

D O I：

10.1038/s41467-019-12446-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4(+) T follicular helper (Tfh) cells are the main subset regulating autoreactive B cells. Here we report a CXCR5(+)PD1(+) Tfh subset of CD8(+) T cells whose development and function are negatively modulated by Stat5. These CD8(+) Tfh cells regulate the germinal center B cell response and control autoantibody production, as deficiency of Stat5 in CD8 T cells leads to an increase of CD8(+) Tfh cells, resulting in the breakdown of B cell tolerance and concomitant autoantibody production. CD8(+) Tfh cells share similar gene signatures with CD4(+) Tfh, and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study thus highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance.

引用

页数：15

共 72 条

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