T-cell Numbers and Antigen-specific T-cell Function Follow Different Circadian Rhythms

Circadian rhythms play an important role in modulating cellular immune responses. The present study was performed to characterise circadian variations in lymphocyte numbers and antigen-specific T-cell functionality in healthy individuals under physiological conditions. Blood leukocyte populations of six healthy volunteers were quantified over 24 h. In addition, antigen-specific T-cell functionality was analysed directly ex vivo from whole blood using flow cytometry based on intracellular cytokine induction after a 6-hour stimulation with adenovirus antigen and Staphylococcus aureus enterotoxin B (SEB), respectively. T-cell numbers and reactivity were stable during daytime, whereas a significant increase was observed during late evening and early morning hours. The percentage of T cells reacting towards adenovirus antigen and SEB showed a 1.76 +/- 0.55-fold (p = 0.0002) and a 1.42 +/- 0.33-fold (p = 0.0002) increase, respectively. Dynamics in T-cell reactivity were independent of the mode of antigen stimulation and inversely correlated with plasma levels of endogenous cortisol. Interestingly, peak frequencies of reactive T cells occurred late in the evening and did not directly coincide with peak numbers of bulk T cells that were observed in the early morning hours. Taken together, our data reveal a circadian regulation of T-cell immune responses in the peripheral blood of humans under physiological conditions. This knowledge may be of practical consequence for the timing of blood sampling for functional T-cell assays as well as for immunosuppressive drug intake after organ transplantation, where T-cell function may be influenced not only by drug-mediated inhibition but also by circadian fluctuations in T-cell reactivity.