TY - JOUR T1 - Gα<sub>s</sub>-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells JF - The Journal of Experimental Medicine JO - J Exp Med SP - 517 LP - 526 DO - 10.1084/jem.20181169 VL - 216 IS - 3 AU - Dimitrov, Stoyan AU - Lange, Tanja AU - Gouttefangeas, Cécile AU - Jensen, Anja T.R. AU - Szczepanski, Michael AU - Lehnnolz, Jannik AU - Soekadar, Surjo AU - Rammensee, Hans-Georg AU - Born, Jan AU - Besedovsky, Luciana Y1 - 2019/03/04 UR - http://jem.rupress.org/content/216/3/517.abstract N2 - 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). ER -