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- Title
Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8<sup>+</sup> T cell responses during chronic infection.
- Authors
Kao, Charlly; Oestreich, Kenneth J; Paley, Michael A; Crawford, Alison; Angelosanto, Jill M; Ali, Mohammed-Alkhatim A; Intlekofer, Andrew M; Boss, Jeremy M; Reiner, Steven L; Weinmann, Amy S; Wherry, E John
- Abstract
T cell exhaustion has a major role in failure to control chronic infection. High expression of inhibitory receptors, including PD-1, and the inability to sustain functional T cell responses contribute to exhaustion. However, the transcriptional control of these processes remains unclear. Here we demonstrate that the transcription factor T-bet regulated the exhaustion of CD8+ T cells and the expression of inhibitory receptors. T-bet directly repressed transcription of the gene encoding PD-1 and resulted in lower expression of other inhibitory receptors. Although a greater abundance of T-bet promoted terminal differentiation after acute infection, high T-bet expression sustained exhausted CD8+ T cells and repressed the expression of inhibitory receptors during chronic viral infection. Persistent antigenic stimulation caused downregulation of T-bet, which resulted in more severe exhaustion of CD8+ T cells. Our observations suggest therapeutic opportunities involving higher T-bet expression during chronic infection.
- Subjects
VIRUS diseases; CHRONIC diseases; TRANSCRIPTION factors; MEMBRANE proteins; T cell receptors; GENE expression; CELL differentiation
- Publication
Nature Immunology, 2011, Vol 12, Issue 7, p663
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2046