Cortisol and epinephrine control opposing circadian rhythms in T cell subsets

Blood. 2009 May 21;113(21):5134-43. doi: 10.1182/blood-2008-11-190769. Epub 2009 Mar 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Catecholamines / physiology
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / immunology*
  • Epinephrine / physiology*
  • Gene Expression Regulation
  • Humans
  • Hydrocortisone / physiology*
  • Immunity
  • Lymphocyte Count
  • Receptors, CXCR4 / genetics
  • T-Lymphocyte Subsets / cytology*


  • CXCR4 protein, human
  • Catecholamines
  • Receptors, CXCR4
  • Hydrocortisone
  • Epinephrine