CD8⁺ T cell-derived Fgl2 regulates immunity in a cell-autonomous manner via ligation of FcγRIIB.

ABSTRACT: The regulatory circuits dictating CD8⁺ T cell responsiveness versus exhaustion during anti-tumor immunity are incompletely understood. Here we report that tumor-infiltrating antigen-specific PD-1⁺ TCF-1^- CD8⁺ T cells express the immunosuppressive cytokine Fgl2. Conditional deletion of Fgl2 specifically in mouse antigen-specific CD8⁺ T cells prolongs CD8⁺ T cell persistence, suppresses phenotypic and transcriptomic signatures of T cell exhaustion, and improves control of the tumor. In a mouse model of chronic viral infection, PD-1⁺ CD8⁺ T cell-derived Fgl2 also negatively regulates virus-specific T cell responses. In humans, CD8⁺ T cell-derived Fgl2 is associated with poorer survival in patien

SUBMITTER: Bennion KB 

PROVIDER: S-EPMC11190225 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature