Regulation of Anti-viral T Cell Responses by Tumor Suppressor TSC1

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.