PD-1 expressing islet-specific CD4⁺ T cells promote bystander tolerance and prevent autoimmunity.

ABSTRACT: Loss of T-cell tolerance to multiple islet antigens is a key feature of autoimmune type 1 diabetes. In this study, we investigated the requirement for programmed death 1 (PD-1) expression by CD4⁺ T cells in the maintenance of self-tolerance via bystander suppression of autoreactive CD8⁺ T cells using nonobese diabetic mice. We used CRISPR/Cas9 to selectively knockout PD-1 in islet antigen-specific BDC2.5 CD4⁺ T cells and observed the impact on bystander tolerance of 8.3 CD8⁺ T cells, specific for a different islet antigen. Loss of PD-1 promoted the proliferation, Th1-like effector-memory phenotype, islet infiltration and expression of cytotoxic markers by BDC2.5 cells. PD-1-deficient BDC2.5 cells were impaired in their regulation of 8.3 cells, wh

SUBMITTER: Loaiza Naranjo JD 

PROVIDER: S-EPMC12392717 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature