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

AUTOR(ES)

Liao, Jia-Jun

FONTE

The Federation of American Societies for Experimental Biology

RESUMO

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, prevented anti-S1P1 Ab suppression of S1P1 signaling and T-cell chemotaxis to S1P. Human purified anti-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.

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