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Cutting Edge |
* Departments of Medicine and Microbiology-Immunology, University of California Medical Center, San Francisco, CA 94143; and
Ceretek, LLC, Alameda, CA 94502
Murine CD4 and CD8 T cells express predominantly types 1 and 4 sphingosine 1-phosphate (S1P) G protein-coupled receptors (designated S1P1 and S1P4 or previously endothelial differentiation gene-encoded 1 and 6) for S1P, which has a normal plasma concentration of 0.1–1 µM. S1P now is shown to enhance chemotaxis of CD4 T cells to CCL-21 and CCL-5 by up to 2.5-fold at 10 nM to 0.1 µM, whereas 0.3–3 µM S1P inhibits this chemotaxis by up to 70%. Chemotaxis of S1P1, but not S1P4, transfectants to CXCL1 and CXCL4 was similarly affected by S1P. Activation of CD4 T cells, which decreases S1P receptor expression, suppressed effects of S1P on chemotaxis. Pretreatment of labeled CD4 T cells with S1P before reintroduction into mice inhibited by a maximum of 75% their migration into chemokine-challenged s.c. air pouches. The S1P-S1P1 receptor axis thus controls recruitment of naive T cells by maintaining their response threshold to diverse lymphotactic factors.
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