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

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 β ₂ -integrins. Gα _s -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 β ₂ -integrins—we show that the Gα _s -coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E ₂ , PGD ₂ , 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 Gα _s -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 Gα _s -coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).