ABSTRACT
OKT3 monoclonal antibody to human T cells inhibits the target cell lysis mediated by allogeneic cytotoxic T cells and the generation of these effector cells in mixed lymphocyte culture. This marked inhibition of cell-mediated lysis is not found with other monoclonal antibodies also reactive with cell surface antigens of human T cells (OKT1, OKT4, OKT5, OKT6, OKT8, and OKT11). OKT3 antibody is mitogenic and this effect appears to require receptor activation in that it occurs at low concentrations (10(-12) M range) of OKT3 antibody, requires intact OKT3 IgG, and is inhibited by a factor(s) in human plasma. By contrast, the inhibition of allogeneic cell-mediated lysis by OKT3 antibody appears to be due to steric hindrance in that it requires higher concentrations of OKT3 antibody (10(-8) M range), Fab fragments retain approximately 10% activity, and inhibition is demonstrable in the presence of human plasma. These findings are consistent with the suggestion that OKT3 antibody reacts with the human T-cell antigen-recognition structure.
Subject(s)
Antibodies/immunology , Antigens, Surface/immunology , Epitopes , T-Lymphocytes/immunology , Adult , Animals , Antigen-Antibody Complex , Humans , Hybrid Cells/immunology , Immunoassay , Immunoglobulin Fab Fragments/immunology , Immunoglobulin G , MiceABSTRACT
Human alloreactive cytotoxic T lymphocytes (CTLs) were generated in culture by stimulating peripheral blood lymphocytes against lymphocytes of unrelated donors. OKT3 monoclonal antibody, which reacts with all human peripheral T cells, inhibited more than 50% of the lysis of the allogeneic cells by the CTLs in the four-hour cytotoxicity assay at a concentration of 1 microgram ml-1. OKT4, which reacts with inducer/helper T cells, did not demonstrate this effect. OKT5 and OKT8, both of which react with cytotoxic/suppressor T cells, had a small but distinct inhibitory effect (about 20-30% maximally). OKT3 antibody is also known to induce mitogenesis of peripheral T cells, but this mitogenic effect is probably of itself not the cause of the inhibitory effect of OKT3 on CTLs. Human plasma abolished OKT3-induced mitogenesis of T cells but not OKT3-mediated inhibition of CTL activity. In addition, there exist conditions that allow both full mitogenesis and intact CTL activity, suggesting CTLs can maintain cytolytic activity under mitogenic conditions. The generation of CTLs in the 6-day mixed lymphocyte culture was also inhibited by OKT3. Several possible mechanisms for this effect are discussed.
Subject(s)
Antibodies, Monoclonal , Cytotoxicity, Immunologic , T-Lymphocytes/immunology , Concanavalin A/pharmacology , Humans , Immunity, Cellular , Lymphocyte Culture Test, Mixed , Mitogens/pharmacologyABSTRACT
Light microscopy and a radioassay detected no significant difference in adherence of Kanagawa-positive and Kanagawa-negative strains of Vibrio parahaemolyticus to human epithelial cell lines.