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FASEB J. 2009 Jun;23(6):1786-96. doi: 10.1096/fj.08-124891. Epub 2009 Jan 21.

Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor.

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1
Department of Medicine, University of California San Francisco, San Francisco, California, USA.

Abstract

Anti-lymphocyte antibodies (Abs) that suppress T-cell chemotactic and other responses to sphingosine 1-phosphate (S1P), but not to chemokines, were found in a lymphopenic patient with recurrent infections. Lymphocyte type 1 S1P receptor (S1P(1)) that transduces S1P chemotactic stimulation was recognized by patient Abs in Western blots of T cells, S1P(1) transfectants, and S1P(1)-hemagglutinin purified by monoclonal anti-hemagglutinin Ab absorption. The amino terminus of S1P(1), but not any extracellular loop, prevented anti-S1P(1) Ab suppression of S1P(1) signaling and T-cell chemotaxis to S1P. Human purified anti-S1P(1) Abs decreased mouse blood lymphocyte levels by a mean of 72%, suppressed mouse T-cell chemotaxis to S1P in vivo, and significantly reduced the severity of dextran sodium sulfate-induced colitis in mice. Human Abs to the amino terminus of S1P(1) suppress T-cell trafficking sufficiently to impair host defense and provide therapeutic immunosuppression.

PMID:
19158154
PMCID:
PMC2698662
DOI:
10.1096/fj.08-124891
[Indexed for MEDLINE]
Free PMC Article
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