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Immunity. 2009 Aug 21;31(2):309-20. doi: 10.1016/j.immuni.2009.06.019. Epub 2009 Aug 6.

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

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1
Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, PA 19104, USA.

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.

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PMID:
19664943
PMCID:
PMC2747257
DOI:
10.1016/j.immuni.2009.06.019
[Indexed for MEDLINE]
Free PMC Article

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