STING signaling modulates CD8 T cell memory fitness via differential TCR signaling

Abstract

STING functions as a critical mediator of DNA sensing to direct both innate immune responses as well as functioning to maintain cellular homeostasis. While STING has been extensively investigated in innate cells, autoimmune disorders, and cancer, little is known about STING's role in CD8 T cell processes. We show here that high levels of STING signaling induce potent reductions in CD8 T cell memory formation. STING functions in both a T cell intrinsic and T cell extrinsic manner to regulate the survival of T cells as they progress to a memory phenotype. Moreover, TCR signal strength regulates the sensitivity of T cells to STING-induced cellular apoptosis and the ability of T cells to join the pool of memory cells. Our data suggests that STING signaling pushes ER stress and death through the UPR to regulate T cell memory. Together, these provide insight into how enhanced STING signals and TCR signaling coalesce to regulate the T cell memory pool and the efficacy of the immune response.