Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control.

ABSTRACT: PD-1 is a key negative regulator of CD8⁺ T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects. Here, we functionally interrogated the epigenetic regulation of PD-1 using a mouse model with deletion of an exhaustion-specific PD-1 enhancer. Enhancer deletion exclusively alters PD-1 expression in CD8⁺ T cells in chronic infection, creating a 'sweet spot' of intermediate expression where T cell function is optimized compare

SUBMITTER: Weiss SA 

PROVIDER: S-EPMC11528687 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature