The forkhead transcription factor, Foxo1, may coordinate naïve CD8+ T cell homeostasis with energy availability in mice. (LYM4P.758)

Abstract

Abstract The naïve CD8+ T cell population must be large enough so that sufficient diversity exists to respond to potential pathogens, yet not so large as to unnecessarily drain an organism’s resources. Thus, we propose that a molecular network links the size of the naïve CD8+ T cell pool with energy availability. We report that short-term calorie restriction in C57BL/6 mice resulted in reduced numbers of naïve CD8+ T cells which efficiently engaged survival signals and minimized energy usage. For example, calorie restricted naïve CD8+ T expressed higher levels of CD8 and CD127 than ad libitum cells, both of which are responsible for receiving homeostatic survival signals in vivo. Naïve CD8+ T cells isolated from calorie restricted mice also experienced less death-by-neglect and engaged in less glycolysis than cells isolated from mice fed ad libitum. Finally, neither the size of the naïve CD8+ T cell pool nor the sensitivity of those cells to death-by-neglect were affected by calorie restriction in the absence of the forkhead transcription factor, Foxo1, indicating that Foxo1 may be involved in synchronizing the size of the naïve CD8+ T cell pool with energy availability.