title: Transduction of multiple effects of sphingosine 1-phosphate (S1P) on T cell functions by the S1P1 G protein-coupled receptor.
abstract: Sphingosine 1-phosphate (S1P) in blood, lymph, and immune tissues stimulates and regulates T cell migration through their S1P(1) (endothelial differentiation gene encoded receptor-1) G protein-coupled receptors. We show now that S1P(1)Rs also mediate suppression of T cell proliferation and cytokine production. Uptake of [(3)H]thymidine by mouse CD4 T cells stimulated with anti-CD3 mAbs plus either anti-CD28 or IL-7 was inhibited up to 50% by 10(-9)-10(-6) M S1P. Suppression by S1P required Ca(2+) signaling and was reduced by intracellular cAMP. S1P decreased CD4 T cell generation of IFN-gamma and IL-4, without affecting IL-2. A Th1 line from D011.10 TCR transgenic mice without detectable S1P(1) was refractory to S1P until introduction of S1P(1) by retroviral transduction. S1P then evoked chemotaxis, inhibited chemotaxis to CCL-5 and CCL-21, and suppressed Ag-stimulated proliferation and IFN-gamma production. Thus, S1P(1) signals multiple immune functions of T cells as well as migration and tissue distribution.
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008246:Lysophospholipids; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D049312:Receptors, Lysophospholipid; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D007376:Interleukin-2; D008246:Lysophospholipids; D011948:Receptors, Antigen, T-Cell; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D015847:Interleukin-4; C060506:sphingosine 1-phosphate; D007371:Interferon-gamma; D013110:Sphingosine