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- Title
Coregulation of CD8<sup>+</sup> T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
- Authors
Blackburn, Shawn D; Shin, Haina; Haining, W Nicholas; Zou, Tao; Workman, Creg J; Polley, Antonio; Betts, Michael R; Freeman, Gordon J; Vignali, Dario A A; Wherry, E John
- Abstract
T cell exhaustion often occurs during chronic infection and prevents optimal viral control. The molecular pathways involved in T cell exhaustion remain poorly understood. Here we show that exhausted CD8+ T cells are subject to complex layers of negative regulation resulting from the coexpression of multiple inhibitory receptors. Exhausted CD8+ T cells expressed up to seven inhibitory receptors. Coexpression of multiple distinct inhibitory receptors was associated with greater T cell exhaustion and more severe infection. Regulation of T cell exhaustion by various inhibitory pathways was nonredundant, as blockade of the T cell inhibitory receptors PD-1 and LAG-3 simultaneously and synergistically improved T cell responses and diminished viral load in vivo. Thus, CD8+ T cell responses during chronic viral infections are regulated by complex patterns of coexpressed inhibitory receptors.
- Publication
Nature Immunology, 2009, Vol 10, Issue 1, p29
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni.1679