Faculty Collaboration Database

CXCR5⁺PD-1⁺ follicular helper CD8 T cells control B cell tolerance. Nat Commun 2019 Sep 27;10(1):4415

Date

09/29/2019

Pubmed ID

31562329

Pubmed Central ID

PMC6765049

DOI

10.1038/s41467-019-12446-5

Scopus ID

2-s2.0-85072692451 (requires institutional sign-in at Scopus site)   53 Citations

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.

Author List

Chen Y, Yu M, Zheng Y, Fu G, Xin G, Zhu W, Luo L, Burns R, Li QZ, Dent AL, Zhu N, Cui W, Malherbe L, Wen R, Wang D

Authors

Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Nan Zhu PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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