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A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control. Cell Rep 2015 Nov 10;13(6):1118-1124

Date

11/04/2015

Pubmed ID

26527008

Pubmed Central ID

PMC4859432

DOI

10.1016/j.celrep.2015.09.069

Scopus ID

2-s2.0-84946826734   36 Citations

Abstract

Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue "unhelped" CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells "help" the CD8 response during chronic infection via IL-21-induced BATF expression.

Author List

Xin G, Schauder DM, Lainez B, Weinstein JS, Dai Z, Chen Y, Esplugues E, Wen R, Wang D, Parish IA, Zajac AJ, Craft J, Cui W

Authors

Weiguo Cui PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




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

Animals
Basic-Leucine Zipper Transcription Factors
CD8-Positive T-Lymphocytes
Cells, Cultured
Interferon Regulatory Factors
Interleukins
Mice
Mice, Inbred C57BL
Positive Regulatory Domain I-Binding Factor 1
Transcription Factors
Virus Diseases
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5