Complement inhibits immune responses: C3 preparations inhibit the generation of human cytotoxic T lymphocytes

C3 fragments have been shown to inhibit mitogen- and antigen-induced human lymphocyte blastogenesis. In this study, C3 preparations and a small fragment of C3 (contained in a preparation called Fraction 2) were examined for their capacity to regulate cytotoxic T lymphocytes (CTL) and proliferative mixed lymphocyte responses (MLR). We found that both preparations inhibited the generation of allogeneic human CTL as well as MLR in a dose-related manner. In contrast, Fraction 1, which contained native C3 and C3b, did not inhibit the generation of CTL nor did it inhibit the MLR. The kinetics of inhibition of proliferation were divergent from the kinetics of inhibition of CTL generation; the active preparations inhibited proliferation significantly when added as late as day 5 of a 6-day culture, whereas no inhibition of CTL generation was seen when these preparations were added after day 3 of culture. Cultures in which C3 preparations caused complete inhibition of CTL generation had normal levels of the nonspecific, anomalous killer cell activity, as assayed on K 562 target cells. Furthermore, C3 preparations and Fraction 2 had no effect on the lytic function of differentiated CTL, on "spontaneous" natural killer cell activity or on interferon-induced augmentation of natural killer cell activity. These findings indicate that C3 fragments may play a negative role in the regulation of CTL responses.