Submitted November 20, 2008
Accepted March 9, 2009
Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets
Stoyan Dimitrov, Christian Benedict, Dennis Heutling, Jurgen Westermann, Jan Born, and Tanja Lange*
Department of Neuroendocrinology, University of Lubeck, Lubeck, Germany
Department of Anatomy, University of Lubeck, Lubeck, Germany
* Corresponding author; email: lange{at}kfg.uni-luebeck.de.
Pronounced circadian rhythms in numbers of circulating T-cells reflect a systemic control of adaptive immunity whose mechanisms are obscure. Here, we show that circadian variations in T-cell subpopulations in human blood are differentially regulated via release of cortisol and catecholamines. Within the CD4+ and CD8+ T-cell subsets, naive cells show pronounced circadian rhythms with a daytime nadir, whereas (terminally differentiated) effector CD8+ T-cell counts peak during daytime. Naive T-cells were negatively correlated with cortisol rhythms, decreased after low-dose cortisol infusion, and showed highest expression of CXCR4 which was upregulated by cortisol. Effector CD8+ T-cells were positively correlated with epinephrine rhythms, increased after low-dose epinephrine infusion, and showed highest expression of 
-adrenergic and fractalkine receptors (CX3CR1). Daytime increases in cortisol via CXCR4 likely acts to redistribute naive T-cells to bone marrow whereas daytime increases in catecholamines via -adrenoceptors and, possibly, a suppression of fractalkine signaling promote mobilization of effector CD8+ T-cells from the marginal pool. Thus, activation of the major stress hormones during daytime favor immediate effector defense but diminish capabilities for initiating adaptive immune responses.
