Role of Tumor Suppressor TSC1 in CD8T Cell Immune Responses upon Viral Infection

초록

The mechanistic target of rapamycin (mTOR) integrates various immune responses such as allergy, inflammation, and infection. Tuberous sclerosis 1 (TSC1)/TSC2 complex is a major negative regulator of mTOR complex 1 (mTORC1) signaling pathway. Many studies have elucidated the roles of mTORC1 in T cell biology including survival, development, and function. Here, we demonstrate that TSC1 plays a critical role in immunity against viral infection. Deletion of TSC1 in T cell lineages results in decreased viral clearance upon lymphocytic choriomeningitis virus (LCMV) infection in mice. LCMV-induced CD8T cell expansion was impaired by TSC1 deficiency, whereas the proportions of viral antigen-specific CD8T cells and their cytokine production were comparable to wild-type controls. These data suggest that hyperactivation of mTORC1 impairs CD8T cell immune responses against viral infection.