PD-1 regulates CD4⁺ T cell-mediated CD8⁺ T cell responses in the brain to balance viral control and neuroinflammation.

ABSTRACT: Programmed cell death protein 1 (PD-1) is expressed by T cells during progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by the human-only JC polyomavirus. Why PD-1 blockade finds variable success in PML patients is unclear. Brain CD4⁺ and CD8⁺ T cells are PD-1^high during mouse polyomavirus (MuPyV) encephalitis. Here, we show that PD-1 loss during MuPyV infection acts in a brain-autonomous manner to increase the magnitude of brain-infiltrating CD4⁺ and CD8⁺ T cells and the function of virus-specific CD8⁺ T cells; in concert, brain virus levels decline and neuroinflammation increases. Deletion of PD-1 in CD4⁺ T cells, but not CD8⁺ T cells, recapitulates effects of g

SUBMITTER: Butic AB 

PROVIDER: S-EPMC12707290 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature