Circadian variations of various aspects of the immune system have been described. However, the circadian control of T cells has been relatively unexplored. Here, we investigated the role of circadian clocks in regulating CD8 T cell response to antigen presentation by dendritic cells (DCs). The in vivo CD8 T cell response following vaccination with DCs loaded with the OVA 257-264 peptide antigen (DC-OVA) leads to a higher expansion of OVA-specific T cells in response to vaccination done in the middle of the day, compared to other time points. This rhythm was dampened when DCs deficient for the essential clock gene Bmal1 were used and abolished in mice with a CD8 T cell-specific Bmal1 deletion. Thus, we assessed the circadian transcriptome of CD8 T cells and found an enrichment in the daytime of genes and pathways involved in T cell activation. Based on this, we investigated early T cell activation events. Three days postvaccination, we found higher T cell activation markers and related signaling pathways (including IRF4, mTOR, and AKT) after a vaccination done during the middle of the day compared to the middle of the night. Finally, the functional impact of the stronger daytime response was shown by a more efficient response to a bacterial challenge at this time of day. Altogether, these results suggest that the clock of CD8 T cells modulates the response to vaccination by shaping the transcriptional program of these cells and making them more prone to strong and efficient activation and proliferation according to the time of day.

Numerous physiological processes vary according to the time of the day in mammals, including the immune defense mechanisms. These circadian rhythms are generated by circadian clocks located in most cell types including cells of the immune system. Recent research has shown that circadian clock function is key to maintaining the homeostasis of the immune system. Indeed, the development and differentiation of different immune cells, and their trafficking between tissues, rely on proper clock function. Disruption of immune system homeostasis can lead to the development of pathological processes such as inflammation or autoimmune diseases. Circadian clocks also control the response of the immune system to inflammatory challenges and infections, and clock dysfunction can provoke or enhance disease. This review focuses on the role of circadian clocks in the homeostasis of immune cells, such as cell recirculation in the peripheral blood and tissues, as well as in the context of inflammation in response to infectious challenges or autoimmune disorders.