Activation-regulated expression and chemotactic function of sphingosine 1-phosphate receptors in mouse splenic T cells.

Sphingosine 1-phosphate (S1P) from platelets and macrophages stimulates migration and enhances survival of T cells. Mouse spleen CD4 and CD8 T cells are shown to express predominantly S1P1 (Edg-1) and S1P4 (Edg-6) G-protein-coupled receptors with only minimal representation of S1P2, S1P3, and S1P5. At and below plasma concentrations of healthy mammals (1 nM-1 microM), S1P evokes trans-Matrigel chemotaxis of mouse CD4 and CD8 T cells and recruits T cells into subcutaneous air pouches. T cell receptor-mediated activation of CD4 T cells suppresses expression of S1P1 and S1P4 receptors and eliminates their chemotactic responses to S1P. The immunoregulator FTY720, a structural homologue of S1P, lacks T cell chemotactic activity and competitively inhibits T cell chemotactic responses to S1P in vitro and in vivo. S1P may be a distinctive contributor to compartmental immunity by attracting naïve and memory T cells preferentially over activated effector T cells.