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

Yuhong Chen; Mei Yu; Yongwei Zheng; Guoping Fu; Gang Xin; Wen Zhu; Lan Luo; Robert Burns; Quan-Zhen Li; Alexander L Dent; Nan Zhu; Weiguo Cui; Laurent Malherbe; Renren Wen; Demin Wang

doi:10.1038/s41467-019-12446-5

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

Nat Commun. 2019 Sep 27;10(1):4415. doi: 10.1038/s41467-019-12446-5.

Authors

Yuhong Chen¹, Mei Yu¹, Yongwei Zheng¹, Guoping Fu¹, Gang Xin¹, Wen Zhu^{1

2}, Lan Luo^{1

3}, Robert Burns¹, Quan-Zhen Li⁴, Alexander L Dent⁵, Nan Zhu¹, Weiguo Cui¹, Laurent Malherbe⁶, Renren Wen¹, Demin Wang^{7

8

9}

Affiliations

¹ Blood Research Institute, Versiti, Milwaukee, WI, USA.
² Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.
³ Chinese PLA General Hospital, Beijing, China.
⁴ Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁵ Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶ Toxicology Division, Eli Lilly, Indianapolis, IN, USA.
⁷ Blood Research Institute, Versiti, Milwaukee, WI, USA. [email protected].
⁸ Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA. [email protected].
⁹ Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, China. [email protected].

Abstract

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Autoantibodies / immunology
Autoantibodies / metabolism
Autoimmune Diseases / genetics
Autoimmune Diseases / immunology
Autoimmune Diseases / metabolism
B-Lymphocytes / immunology*
B-Lymphocytes / metabolism
CD40 Antigens / genetics
CD40 Antigens / immunology
CD40 Antigens / metabolism
CD40 Ligand / genetics
CD40 Ligand / immunology
CD40 Ligand / metabolism
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / metabolism
Gene Expression Profiling / methods
Humans
Immune Tolerance / genetics
Immune Tolerance / immunology*
Programmed Cell Death 1 Receptor / genetics
Programmed Cell Death 1 Receptor / immunology*
Programmed Cell Death 1 Receptor / metabolism
Receptors, CXCR5 / genetics
Receptors, CXCR5 / immunology*
Receptors, CXCR5 / metabolism
STAT5 Transcription Factor / genetics
STAT5 Transcription Factor / immunology
STAT5 Transcription Factor / metabolism
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
T-Lymphocytes, Helper-Inducer / immunology*
T-Lymphocytes, Helper-Inducer / metabolism

Substances

Autoantibodies
CD40 Antigens
CXCR5 protein, human
Programmed Cell Death 1 Receptor
Receptors, CXCR5
STAT5 Transcription Factor
CD40 Ligand

Abstract

Publication types

MeSH terms

Substances

Grants and funding