Human Lymphocyte Antibody-dependent Cell-mediated Cytotoxicity (ADCC) Toward Human Red Blood Cells

Abstract

Previous investigations involving mononuclear cell antibody-dependent cell-mediated cytotoxicity (ADCC) toward human red cell (RBC) targets indicated that monocytes but not lymphocytes are able to produce erythrocyte lysis. We reexamined this reported insensitivity of human RBC to lymphocyte cytotoxicity using a variety of human RBC targets and a wide range of antisera to various erythrocyte antigens. We observed, as did other investigators, that normal O+ red cells (R1R2-CDē/ c ¯ DE) pretreated with small amounts of typical anti-D serum were quite susceptible to monocyte lysis but were completely resistant to lymphocyte ADCC. However, four other human RBC-antibody combinations were found to mediate striking lymphocyte and monocyte cytotoxicity. These included (1) -D-cells plus typical anti-D, (2) normal O+ cells (R1R2) plus Ripley anti-CD, (3) papa in-pre treated normal O+ cells plus small amounts of anti-D and (4) normal 0+ cells plus very large amounts of anti-D. These findings show that human RBC are not uniquely resistant to lymphocyte ADCC and that antibody density and/or distribution on the target cell surface may be very important to cytotoxicity by leukocytes. The basic characteristics of lymphocyte ADCC toward human RBC are similar to those reported for nucleated targets. Cytolysis is temperature-dependent and rapid, with nearly all erythrocyte lysis occurring in the first 4 hr of incubation. Extent of target cell destruction is positively related to the effector/target ratio and the amount of antibody bound to the erythrocyte surface. Further evidence showing the antibody-dependent cell contact-mediated nature of the cytolytic event includes inhibition of ADCC with nonspecific immunoglobulin and data obtained from “innocent bystander” studies.