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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Kao C,Oestreich KJ,Paley MA,Crawford A,Angelosanto JM,Ali MA,Intlekofer AM,Boss JM,Reiner SL,Weinmann AS,Wherry EJdoi
10.1038/ni.2046subject
Has Abstractpub_date
2011-05-29 00:00:00pages
663-71issue
7eissn
1529-2908issn
1529-2916pii
ni.2046journal_volume
12pub_type
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