Autophagy-deficient CD8~+CTL Exhibit Increased Activation Level And Stronger Anti-tumor Activity

Autophagy is a major catabolic process in which intracellular membrane structures, protein complexes, and lysosomes can form lysoautophagosomes to degrade and renew cytoplasmic components. Autophagy is a physiological process-to maintain cellular homeostasis, and thus alterations of autophagy activity may lead to diverse pathological consequences. CD8+T cell, as an important part of adaptive immune system, plays an important role in eliminating the virus-infected cells and tumor cells. However, the role of autophagy in the activation and cytotoxicity in CD8+T cells still remain unknown. Here, we utilized Atg3 conditional knock-out mice to determine how autophagy control the activation and function of CD8+T cell and further elucidate its physiological significant.In our mice model, we found autophagy-deficient CTL exhibited higher cytolytic activity both in vivo and in vitro. Furthermore, autophagy-deficient CTL showed stronger anti-tumor effect in vivo and therefore resulted in prolonged survival of tumor-bearing mice. We further analyzed the mechanism for the increased CTL cytotoxicity, and found the autophagy-deficient CD8+T cells is susceptible to be activated, evidence as higher level of activation markers and proliferation activity. The higher activation level of autophagy-deficient CTL also resulted in high expression level of perform and granzyme B. Therefore, we hypothesized autophagy controlled the cytotoxicity of CTL through altering the activation of CD8+T cells. Further study is needed for elucidate the mechanism of autophagy to regulate the activation of CD8+ T cells.