Immunoregulatory effects of C3 and its major cleavage fragments

The immunoregulatory effects of highly purified C3 and its major cleavage fragments on in vitro responses of human peripheral blood mononuclear cells (PBMC) were examined. Polyclonal immunoglobulin production induced by PWM and T-cell proliferation stimulated by tetanus toxoid in human PBMC were inhibited by human C3b. This effect occurred in a dose range of 10(-6) to 10(-8) M and was observed in cultures containing human serum but not under serum-free conditions. This noncytotoxic suppression did not appear to be mediated by prostaglandin release nor by interference with antigen uptake and presentation by monocytes. In contrast, the addition of C3a resulted in a mild enhancement of immunoglobulin production and T-cell proliferation. This effect, however, was observed only under serum-free conditions and, thus, may not have physiologic importance. The native C3, from which the above fragments were generated, had no effect on these lymphocyte responses. These results suggest that regulation of immune responses may be one consequence of C3 cleavage during complement activation in vivo.