Cortisol and epinephrine control opposing circadian rhythms in T cell subsets.
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 up-regulated by cortisol. Effector CD8(+) T cells were positively correlated with epinephrine rhythms, increased after low-dose epinephrine infusion, and showed highest expression of beta-adrenergic and fractalkine receptors (CX3CR1). Daytime increases in cortisol via CXCR4 probably act to redistribute naive T cells to bone marrow, whereas daytime increases in catecholamines via beta-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.
Dimitrov
Stoyan
S
Departments of Neuroendocrinology, University of Lübeck, Germany.
Benedict
Christian
C
Heutling
Dennis
D
Westermann
Jürgen
J
Born
Jan
J
Lange
Tanja
T
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002395:Catecholamines / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000276:immunology*; D004837:Epinephrine / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology*; D007109:Immunity; D018655:Lymphocyte Count; D019718:Receptors, CXCR4 / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology*
C527276:CXCR4 protein, human; D002395:Catecholamines; D019718:Receptors, CXCR4; D006854:Hydrocortisone; D004837:Epinephrine