s-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells

J Exp Med. 2019 Mar 4;216(3):517-526. doi: 10.1084/jem.20181169. Epub 2019 Feb 12.


Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)-mediated activation of β2-integrins. Gαs-coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1-the ligand of β2-integrins-we show that the Gαs-coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2, PGD2, and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8+ T cells in a dose-dependent manner. In contrast, sleep, a natural condition of low levels of Gαs-coupled receptor agonists, up-regulates integrin activation compared with nocturnal wakefulness, a mechanism possibly underlying some of the immune-supportive effects of sleep. The findings are also relevant for several pathologies associated with increased levels of Gαs-coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Adult
  • CD18 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / virology
  • Catecholamines / metabolism
  • Cytomegalovirus Infections / metabolism
  • Dinoprostone / metabolism
  • Dinoprostone / pharmacology
  • Epinephrine / pharmacology
  • Epstein-Barr Virus Infections / metabolism
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Activation
  • Male
  • Signal Transduction
  • Sleep / physiology*


  • CD18 Antigens
  • Catecholamines
  • ICAM1 protein, human
  • Intercellular Adhesion Molecule-1
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenosine
  • Dinoprostone
  • Epinephrine