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 mu g/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 mu g/ml) and when added subsequently to the initiation of cultures.