Human CD4-reactive antibodies from SLE patients induce reversible inhibition of polyclonal T lymphocyte proliferation.
We report on isolation of human polyclonal CD4-reactive antibodies of IgM and/or IgG isotypes from several SLE patients. These antibodies bound specifically to CD4-expressing cell lines and to rCD4 in ELISA and immunoblots. Saturation of CD4-binding sites occurred at antibody concentrations between 5 and 15 micrograms/ml. Anti-CD4 antibodies, in a dose-dependent manner, suppressed the proliferative responses of human peripheral blood mononuclear cells (PBMC) to superantigens (Staphylococcal enterotoxins A and B), anti-CD3 antibodies, and mitogens (PWM and Con A, but not PHA). They could also inhibit the proliferation of highly purified human T cells induced by immobilized anti-CD3 antibodies. To promote their effects on T cells, human anti-CD4 antibodies had to be present at lymphocyte cultures before or at the time of priming. There was no significant inhibition when antibodies were added more than 24 h following T cell activation. Substantial evidence that the immunosuppression induced by anti-CD4 antibodies was due to their direct effect on T cells was obtained. Down-regulatory effect of anti-CD4 antibodies could be significantly reversed by addition of exogenous IL-2 and by preincubation with soluble recombinant (r)CD4. Interestingly, at least one affinity-purified anti-CD4 antibody could costimulate the T cell proliferation induced by superantigens or anti-CD3 antibodies, especially when used at subsaturating concentrations (1-4 micrograms/ml) and when added subsequently to the initiation of cultures.
Lenert
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Louis-Charles Simard Research Center, Notre-Dame Hospital, University of Montréal, Québec, Canada.
Lenert
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D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M