The circadian rhythm is tuned by the expression of 'clock' genes, which encode molecules that can exert a strong influence on widespread physiological processes. In the Journal of Immunology, Cermakian and colleagues investigate how the circadian rhythm affects T cell functionality. Mice housed in total darkness to prevent light- and melatonin-dependent triggers show rhythmic expression of the circadian Clock gene in peripheral lymph nodes. T cells show a similar cyclical variation in proliferation, with their highest mitogenic potential late in the day or at night. These cyclical differences in T cell proliferation are lost, however, when Clock is deleted. As a possible explanation for these functional differences, there is also rhythmic expression of the key T cell signaling molecule Zap70. Studies of mice immunized at different times of the day demonstrate variability in the functional differentiation of T cells. This study therefore highlights the potentially far-reaching effects of circadian cycling on immune responsiveness.

J. Immunol. 187, 6291–6300 (2011)