Analysis and reversal of the inhibition of cytophilic antibody receptors produced by antibody.
Administration of hyperimmune antibody to leukemia L1210 to allogeneic mice inhibited the development of macrophage-mediated immunity to L1210 in those hosts. In contrast to immunized mice, animals pretreated with antibody showed rapid activation of their peritoneal macrophages, followed by their disappearance and the inability of the residual peritoneal monocytic cells to attach L1210 cells even in the presence of proved cytophilic antibody to L1210. The inhibitory activity of the antibody, which resided entirely in its IgG2 fraction, was manifested only when the specific antigen (L1210 cells) was also injected within 2 days. Pretreatment with antibody to a different leukemia, EL4, failed to inhibit the monocytic uptake of L1210, but it did inhibit uptake of EL4 by monocytes if injected with its homologous antigen. Restoration of the functional capacity of macrophages was accomplished by injecting 1 X 10-7 bone marrow cells i.v. into "suppressed" mice, but 1.5 X 10-7 thymocytes failed to correct the defect. Significantly, thymocytes antagonized the restorative capability of bone marrow cells when they were injected concomitantly. These results indicate that specific inhibition of cytophilic antibody receptors on monocytes could be accomplished through a direct mechanism involving activation and exhaustion of macrophages and an indirect mechanism, perhaps mediated through "suppressor" thymus-derived cells. Although enhancement of the growth of leukemia cells did not occur, several parallels exist in mice with enhanced growth of different tumors. This inhibiotry phenomenon may thus represent another instance of "blocking" in tumor immunity, where the target of suppressive antibody-antigen is the macrophage as well as the lymphocyte.
D000818:Animals; D000912:Antibodies, Neoplasm; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D001666:Binding Sites, Antibody; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D007111:Immunity, Cellular; D007114:Immunization; D007074:Immunoglobulin G; D007939:Leukemia L1210 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G