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PMID: 19664943 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection.

Immunity ·Vol. 31 ·No. 2 ·2009-08-21 ·Pages 309-20

Shin H, Blackburn SD, Intlekofer AM, Kao C, Angelosanto JM, Reiner SL, Wherry EJ

Abstract

T cell exhaustion is common during chronic infections and can prevent optimal immunity. Although recent studies have demonstrated the importance of inhibitory receptors and other pathways in T cell exhaustion, the underlying transcriptional mechanisms are unknown. Here, we define a role for the transcription factor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection. Blimp-1 repressed key aspects of normal memory CD8(+) T cell differentiation and promoted high expression of inhibitory receptors during chronic infection. These cardinal features of CD8(+) T cell exhaustion were corrected by conditionally deleting Blimp-1. Although high expression of Blimp-1 fostered aspects of CD8(+) T cell exhaustion, haploinsufficiency indicated that moderate Blimp-1 expression sustained some effector function during chronic viral infection. Thus, we identify Blimp-1 as a transcriptional regulator of CD8(+) T cell exhaustion during chronic viral infection and propose that Blimp-1 acts as a transcriptional rheostat balancing effector function and T cell exhaustion.

MeSH Terms
Acute Disease Animals Antigens, CD/immunology,metabolism Antigens, Surface/immunology,metabolism Apoptosis Regulatory Proteins/immunology,metabolism CD8-Positive T-Lymphocytes/immunology,metabolism,virology Cell Differentiation/immunology Chronic Disease Cytotoxicity, Immunologic/immunology GPI-Linked Proteins Granzymes/immunology,metabolism Immunologic Memory/immunology Lymphocytic Choriomeningitis/immunology,virology Lymphocytic choriomeningitis virus/immunology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Positive Regulatory Domain I-Binding Factor 1 Programmed Cell Death 1 Receptor Receptors, Immunologic/immunology,metabolism Signaling Lymphocytic Activation Molecule Family Transcription Factors/genetics,metabolism Virus Diseases/genetics,immunology
Chemicals
Antigens, CD Antigens, Surface Apoptosis Regulatory Proteins CD223 antigen Cd160 protein, mouse Cd244a protein, mouse GPI-Linked Proteins Pdcd1 protein, mouse Prdm1 protein, mouse Programmed Cell Death 1 Receptor Receptors, Immunologic Signaling Lymphocytic Activation Molecule Family Transcription Factors Positive Regulatory Domain I-Binding Factor 1 Granzymes
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shin Haina
Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Blackburn Shawn D
Intlekofer Andrew M
Kao Charlly
Angelosanto Jill M
Reiner Steven L
Wherry E John
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2009.06.019
Published
2009-08-21
Epub
2009-00-06
Pages
309-20
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2747257
Subset
IM
Grants
NIAID NIH HHS · U19 AI083022 · United States
NIAID NIH HHS · R01 AI071309 · United States
NCI NIH HHS · CA10815 · United States
NIAID NIH HHS · R01 AI042370 · United States
NIAID NIH HHS · U19 AI083022-01 · United States
PHS HHS · HHSN26620050030C · United States
NIAID NIH HHS · R01 AI076458-02 · United States
NIAID NIH HHS · R01 AI042370-12 · United States
NIAID NIH HHS · R01 AI071309-04 · United States
NIAID NIH HHS · R01 AI076458 · United States
NIAID NIH HHS · AI071309 · United States
Corrections
CommentIn
PMID: 19699168
External Links
PubMed source DOI: 10.1016/j.immuni.2009.06.019 PMC Full Text View journal details
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