Regulation of the human autologous T cell proliferation by endogenously generated C5a.

The immunomodulating role of endogenously synthesized C5 and subsequently generated C5a was studied in a serum-free human autologous mixed leukocyte reaction (AMLR) using either separated T and non-T cell populations or unfractionated mononuclear leukocytes of human peripheral blood. Monoclonal mouse IgG or Fab fragments against human C5/C5a were used as probes for the evaluation of the biological effects of C5a. The reduction of DNA synthesis after the addition of nanogram amounts of anti-C5/C5a mAb was dose-dependent, reaching maximum levels of 30-50%. Of special importance was the availability of a mAb that recognizes a neoepitope present on C5a and not on serum-derived C5. The demonstration of the specificity of its inhibitory effect suggests that C5 is synthesized under the in vitro conditions employed and that the subsequently generated C5a exerts biological effects on T cell proliferation.