Mitogenic actions of Orthoclone OKT3 on human peripheral blood lymphocytes: effects of monocytes and serum components.
The Orthoclone monoclonal antihuman T lymphocyte antibody, OKT3, induced maximal DNA, RNA and protein synthesis in peripheral mononuclear blood cells (PMBC) at concentrations as low as 10 ng ml-1. This pronounced mitogenic activity was highly dependent on the presence of monocytes: removal of these cells from PMBC suspensions by complement (C)-dependent lysis with the antimonocyte antibody OKM1, completely abrogated the proliferative responsiveness of the remaining lymphocytes. The addition of adherent cells to OKM1-treated PMBC demonstrated the strict monocyte requirement for the mitogenic activity of OKT3. Mitogenic responses to OKT3 were most marked when PMBC were cultured in media containing heat-inactivated fetal calf serum (FCS) but they were considerably weaker in cultures supplemented with heat-inactivated human serum (HS). Moreover, aggregated human IgG and its Fc fragments (but not monomeric IgG and its Fab fragments) inhibited the mitogenicity of OKT3: their inhibition could be explained by stimulation of monocytes, resulting in increased prostaglandin E release, since (a) prostaglandin E2 itself strongly suppressed OKT3 activity and (b) indomethacin blocked the inhibitory effects of aggregated HuIgG. The present data demonstrate that OKT3 shows a particular pattern of mitogenicity: the strict monocyte requirement, the inhibitory effects of HS, aggregated human IgG and prostaglandin E2 were not observed for the phytomitogen PHA.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D001769:Blood; D001798:Blood Proteins / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D008934:Mitogens; D010835:Phytohemagglutinins