According to a recent study published in Proceedings of the National Academy of Sciences, the biological clock influences immune response efficacy. Indeed, CD8 T cells, which are essential to fight infections and cancers, function very differently according to the time of day.

We know that circadian rhythms are generated by "clock genes", which influence most organs and cells--including those of the immune system, whose function varies according to the time of day. Accordingly, circadian rhythms are found for various aspects of physiology, including sleep, nutrition, hormonal activity, and body temperature. These daily rhythms help the body adapt to cyclical changes in the environment, such as seasons and the day and night cycle.

In earlier research, the team had demonstrated that T cells react more or less strongly to a foreign body according to the time of day, but the role of the biological clock in this phenomenon remained unknown. The authors 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, they investigated early T cell activation events. Three days postvaccination, researchers 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.

"Using a mouse vaccine model, we observed that after vaccination, the strength of the CD8 T cell response varied according to the time of day. Conversely, in mice whose CD8 T cells were deficient for the clock gene, this circadian rhythm was abolished, and response to the vaccine was diminished in the daytime," explains the senior author.

"Our study shows that T cells are more prone to be activated at certain times of the day. Identifying the mechanisms through which the biological clock modulates the T cell response will help us better understand the processes that regulate optimal T cell responses. This knowledge will contribute to improving vaccination strategies and cancer immune therapies," states the author.

https://www.mcgill.ca/medicine/channels/news/study-shows-biological-clock-influences-immune-response-efficiency-300885

https://www.pnas.org/content/early/2019/09/10/1905080116