The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness

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Science Immunology  09 Dec 2016:
Vol. 1, Issue 6, eaai8593
DOI: 10.1126/sciimmunol.aai8593

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TCF1 fine-tunes T cell exhaustion

Exhaustion of CD8+ T cells is observed in chronic viral infections and in the tumor microenvironment. Using chronic LCMV infection in mice, Wu et al. report that expression levels of the transcription factor T cell factor 1 (TCF1) determine the degree of T cell exhaustion. TCF1high CD8+ T cells are less exhausted as compared with TCF1low CD8+ T cells, and they play an essential role in controlling viremia in chronically infected mice. Blockade of type I interferon, a driver of T cell exhaustion, promoted expansion of TCF1high CD8+ Tcells. The studies have better defined the molecular features of exhausted T cells and suggest that targeting TCF1-driven pathways could be used to modulate T cell exhaustion.