Regulation of antigen-specific CTL and Th1 cell activation through 5-Hydroxytryptamine 2A receptor

Serotonin (5-Hydroxytryptamine, 5-HT) is one of the most extensively studied neurotransmitters in the central nervous system. Also expressed in peripheral tissues, 5-HT participates in vasoconstriction and in aggregation of platelets through 5-HT(2A) receptor (5-HT2AR). However, there have been few studies regarding the interaction between 5-HT and 5-HT2AR in the immune system. In the current study, we analyzed the role of 5-HT and its 5-HT2AR in the activation of antigen-specific Th1 and cytotoxic T lymphocytes (CTL) in mice. RT-PCR and western blotting analyses confirmed the expression of 5-HT2AR in both CD4 and CD8 T cells. Both antigen-specific and anti-CD3 stimulation of IL-2 and IFN-γ production from these cells were inhibited by a selective 5-HT2AR inhibitor, sarpogrelate hydrochloride. Concanavalin A (ConA) activation of CD4(+) and CD8(+) T cells, which were purified from mouse spleen following depletion of endogenous 5-HT, was enhanced by a selective 5-HT2AR agonist, (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Such DOI-induced T cell activation was nullified by sarpogrelate. Moreover, an ELISPOT study showed that sarpogrelate also reduced antigen-specific induction of both CTL and Th1 cells in vivo following immunization of mice with cognate antigens. These data suggest that antigen-specific Th1 and CTL cells might be regulated by 5-HT signaling through 5-HT2AR on their surfaces and that 5-HT2AR inhibitor might have an immunosuppressive effect in vivo.