期刊
JOURNAL OF IMMUNOLOGY
卷 171, 期 7, 页码 3500-3507出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.7.3500
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- NHLBI NIH HHS [HL 31809] Funding Source: Medline
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 [H-3]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 Ca2+ signaling and was reduced by intracellular cAMP. S1P decreased CD4 T cell generation of IFN-gamma and IL-4, without affecting IL-2. A Thl line from D011.10 TCR transgenic mice without detectable S1P, 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.
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