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.
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.
Makoto
M
Inoue
Takahiro
T
Okazaki
Takako
T
Kitazono
Machiko
M
Mizushima
Masami
M
Omata
Shoichi
S
Ozaki
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D012701:Serotonin; D007371:Interferon-gamma