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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-09-2962. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2962v1 101/12/4909    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jin, Y. Articles by Maghazachi, A. A. Search for Related Content PubMed PubMed Citation Articles by Jin, Y. Articles by Maghazachi, A. A. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 4909-4915 IMMUNOBIOLOGY Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation Yixin Jin, Eirunn Knudsen, Ling Wang, Yenan Bryceson, Bassam Damaj, Sandra Gessani, and Azzam A. Maghazachi From the Department of Anatomy and Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway; Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD; Bio-Quant, San Diego, CA; and Instituto Superiore di Sanita, Rome, Italy. Sphingosine 1-phosphate (S1P) is a pleiotropic lysosphingophospholipid stored and secreted by platelets. Using reverse transcription–polymerase chain reaction and flow cytometric analyses, we determined the expression of S1P receptors (S1P1, S1P3, S1P4, and S1P5) in peripheral blood T cells. T cells were induced to proliferate in the presence of phorbol 12-myristate 13-acetate (PMA) plus ionomycin, anti-CD3 plus anti-CD28, and allogeneic immature or mature dendritic cells. This activity was inhibited by the addition of S1P. Enhanced T-cell proliferation was observed when these cells were stimulated with the same stimuli, but were incubated in serum-free media (SFM). Addition of S1P to SFM inhibited the stimulation of T cells induced by T-cell stimuli, suggesting that S1P is an important inhibitory molecule present in the serum. T-cell proliferation was also inhibited by the addition of dihydrosphingosine 1-phosphate (DHS1P), sphingosine, and ceramide; however, the latter 2 sphingolipids required higher concentrations than S1P. Pretreatment of T cells with pertussis toxin (PTX) blocked the inhibitory effect of S1P on activation with PMA plus ionomycin, but not on activation with anti-CD3 plus anti-CD28. This is corroborated with the down-regulation of S1P1 in T cells stimulated with anti-CD3 plus anti-CD28. Similarly, PTX did not affect the inhibitory effect of S1P on T-cell proliferation when dendritic cells were used as stimuli. Further, S1P or DHS1P but not ceramide or sphingosine enhanced rather than decreased secretion of interleukin 2 and interferon by T cells stimulated with anti-CD3 plus anti-CD28. These results show differential effects of S1P on polyclonal T-cell proliferation and cytokine secretion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Wolf, K. Eller, R. Zeiser, C. Durr, U. V. Gerlach, M. Sixt, L. Markut, G. Gastl, A. R. Rosenkranz, and D. 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