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

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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, preventedanti‐S1P 1 Ab suppression of S1P 1 signaling and T‐cell chemotaxis to S1P. Human purifiedanti‐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.—Liao, J.‐J., Huang, M.‐C., Fast, K., Gundling, K., Yadav, M., Van Brocklyn, J.R., Wabl, M.R., Goetzl, E.J. Immunosuppressive human anti‐lymphocyte autoantibodies specific for the type 1 sphingosine 1‐phosphate receptor. FASEB J. 23, 1786–1796 (2009)