Regulation of CD8+ T memory and exhaustion by the mTOR signals
Yao Chen, Ziyang Xu, Hongxiang Sun, Xinxing Ouyang, Yuheng Han, Haihui Yu, Ningbo Wu, Yiting Xie, Bing Su
Abstract
Abstract CD8 + T cells are the key executioners of the adaptive immune arm, which mediates antitumor and antiviral immunity. Naïve CD8 + T cells develop in the thymus and are quickly activated in the periphery after encountering a cognate antigen, which induces these cells to proliferate and differentiate into effector cells that fight the initial infection. Simultaneously, a fraction of these cells become long-lived memory CD8 + T cells that combat future infections. Notably, the generation and maintenance of memory cells is profoundly affected by various in vivo conditions, such as the mode of primary activation (e.g., acute vs. chronic immunization) or fluctuations in host metabolic, inflammatory, or aging factors. Therefore, many T cells may be lost or become exhausted and no longer functional. Complicated intracellular signaling pathways, transcription factors, epigenetic modifications, and metabolic processes are involved in this process. Therefore, understanding the cellular and molecular basis for the generation and fate of memory and exhausted CD8 + cells is central for harnessing cellular immunity. In this review, we focus on mammalian target of rapamycin (mTOR), particularly signaling mediated by mTOR complex (mTORC) 2 in memory and exhausted CD8 + T cells at the molecular level.