Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens

Abstract

Human T lymphocyte subpopulations were recently defined by monoclonal antibodies that recognize cell-surface antigens selectively expressed on functionally distinct T cell subsets. The majority (90%) of the peripheral blood sheep erythrocyte rosette-forming cells carry the OKT3 antigen. Helper cells are OKT4+, whereas cytotoxic/suppressor cells are OKT5+ and OKT8+. The effect of several monoclonal antibodies recognizing T cell antigens on certain proliferative responses of T cells and on the effector phase of the specific T cell-mediated cytotoxicity generated in mixed lymphocyte culture (MLC) was investigated. In the absence of added complement, OKT3 and OKT4 monoclonal antibodies inhibited the proliferative response to phytohemagglutinin (PHA), OKT3 monoclonal antibody inhibited the proliferative response to allogeneic cells in MLC, and OKT3 monoclonal antibody significantly and regularly inhibited the effector phase of the specific T cell-mediated cytotoxicity against allogeneic targets (P < 0.001) in a concentration-dependent manner. The OKT5 and OKT8 monoclonal antibodies, again in the absence of complement, moderately inhibited the specific cell-mediated cytotoxicity. This inhibition was observed in some experiments only. Inhibition of the specific cytotoxicity by these antibodies also was observed in secondary responses. In contrast, again in the absence of added complement, none of these antibodies had an effect on the nonspecific cytotoxicity generated in MLC against K562 [human leukemia cell] targets. The OKT4 antibody in the absence of added complement had no effect on either the specific or nonspecific cytotoxicity. Treatment with OKT3 or OKT8 antibody and complement completely abrogated the specific T cell-mediated cytotoxicity but had no effect on the natural killer-like cytotoxicity against the K562 cells. Treatment with the OKT4 antibody and complement had no effect. The T5/T8 and T3 antigens, present on cytotoxic T lymphocytes, may be involved directly or indirectly in the antigen recognition step(s) or the lytic mechanism of T cell-mediated lympholysis. Nonspecific cytotoxicity against the K562 targets generated in MLC is apparently mediated by cells phenotypically different than those that mediate specific cytotoxicity.