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

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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 (S1P1) that transduces S1P chemotactic stimulation was recognized by patient Abs in Western blots of T cells, S1P1 transfectants, and S1P1‐hemagglutinin purified by monoclonal anti‐hemagglutinin Ab absorption. The amino terminus of S1P1, but not any extracellular loop, preventedanti‐S1P1 Ab suppression of S1P1 signaling and T‐cell chemotaxis to S1P. Human purifiedanti‐S1P1 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 S1P1 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)
Funding Information
  • National Institutes of Health (HL–31809)