Nonrestricted cytotoxicity mediated by interleukin 2-expanded leukocytes is inhibited by anti-LFA-1 monoclonal antibodies (MoAb) but potentiated by anti-CD3 MoAb.
Previous results have shown that in addition to their ability to kill tumor cell lines, peripheral blood leukocytes (PBL) expanded in interleukin 2 (IL-2) can also destroy normal PBL targets. Cold target competition results show that PBL and tumor cells can be destroyed by the same population of IL-2-expanded leukocytes (IEL), with better killing observed for tumor cell targets. Since cytolytic activity of IEL is nonspecific, differential binding of target cells by IEL could determine how well each target cell type can be killed. The binding affinity of IEL, in turn, could be influenced by the accessory molecules expressed on effector and target cells. We tested the effect of MoAb to LFA-1, CD2, CD3, CD4, CD8, and HLA molecules on killing mediated by IEL. Anti-LFA-1 inhibited strongly the killing of normal PBL and to a lesser extent the killing of tumor cells. Anti-CD2, CD3, CD4, CD8, and HLA class I molecules did not inhibit the nonspecific killing; rather, anti-CD3 potentiated the killing of PBL, K562, and Daudi cells. These results support the notion that qualitative and quantitative variations in LFA-1-mediated binding of target cells by IEL could result in differential killing of targets. The possibility of using anti-CD3 to selectively potentiate the killing of tumor cells is discussed.
D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006680:HLA Antigens / Q000276:immunology; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D006680:HLA Antigens; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins