Neurology Central

Could circadian rhythms influence immune response efficiency in mice?


A research team, led by Nicolas Cermakian and Nathalie Labrecque at McGill University (Quebec, Canada), has demonstrated that circadian rhythms in mice could control the extent of CD8 T-cell response to antigen presentation by dendritic cells. The CD8 T cells’ circadian clock is essential for circadian regulation and the cells have been found to be stimulated depending on the time of day. The research has been published in Proceedings of the National Academy of Sciences of the United States of America.

The research team investigated the CD8 T cells’ response to antigens presented by dendritic cells. Vaccination with dendritic cells loaded with the OVA257–264 peptide antigen was revealed to produce a higher level of OVA-specific T cells in the middle of the day compared to the middle of the night.

“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,” explained Cermakian.

The team also indicated that when dendritic cells were lacking the essential clock gene, Bmal1, the rhythm was reduced.

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“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,” said Cermakian.

“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,” explained Labrecque.

The results of this study imply that the clock gene of CD8 T cells regulates the response to vaccination by influencing the transcriptional program of the cells and making them more susceptible to activation depending on the time of day.

Sources: Nobis CC, Laramee GD, Kervezee L, De Sousa DM, Labrecque N, Cermakian N. The circadian clock of CD8 T cells modulates their early response to vaccination and the rhythmicity of related signaling pathways. Proc. Natl Acad. Sci. doi:10.1073/pnas.1905080116 (2019) (Epub ahead of print);