Type 1 (S1P1) and type 4 (S1P4) sphingosine 1-phosphate (S1P) G protein-coupled receptors transduce regulation of T cell migration, proliferation and cytokine secretion

S1P is a lysophospholipid with diverse effects on T cell functions. Of the five S1P G protein-coupled receptors, S1P(1) and S1P(4) predominate in T cells. To assess the CD4 T cell subset specificity of SIP effects, S1P(1) and S1P(4) were introduced into DO11.10 Th1 cells and D10G4.1 Th2 cells, respectively. In S1P(1)-DO11.10 cells, S1P evoked chemotaxis directly and inhibited chemotaxis to CCL-5 and CCL-21. In S1P(4)-D10G4.1 T cells, S1P significantly inhibited proliferation and secretion of IL-4, but enhanced IL-10 secretion. S1P neither elicited nor suppressed chemotaxis of S1P(4)-D10G4.1 T cells. FTY720 treatment on CD4 T cells, which downregulates SIP, but not S1P(4) receptors, blocked the chemotaxis effect. Thus, unlike S1P(1), S1P(4) mediates effects of SIP on lymphocyte proliferation and cytokine secretion, but not on migration.