Antibody-dependent cell-mediated cytotoxicity by human lymphocytes: a regulatory role for the sheep red blood cell receptor.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is a cytolytic mechanism whereby unimmunized lymphoid cells lyse antibody-sensitized target cells. The cells mediating ADCC are referred to functionally as killer cells (K cells). K cells are a heterogeneous population of lymphocytes based on cell membrane marker criteria but may be morphologically homogeneous. It is well established that K cells must have an Fc receptor (FcR) appropriate for the class of target cell-bound antibody, and that physical interaction between the K cell's FcR and the Fc portion of target cell-bound antibody is required for the initiation of lysis. Relatively little is known about the regulatory mechanisms presumed to exist and modulate ADCC reactions. We have made 2 observations that led us to investigate the possibility that the sheep erythrocyte (SRBC) receptor (ER) on human cells might be involved as a regulator of ADCC. First, SRBC are more efficiently lysed by human lymphocytes than are other erythrocyte target cells, and second, although nonsensitized bystander cells are usually not lysed during ADCC reactions, SRBC are consistently lysed. Removal of E-rosetting capacity of lymphocytes by trypsin treatment selectively decreases lysis of IgG sensitized SRBC. Furthermore, lysis of nonsensitized bystander SRBC is also inhibited by trypsin treatment of effector cells. ADCC is also decreased by blocking the ER with simple sugars or monoclonal antibody so that E-rosettes are inhibited. In contrast to trypsin treatment, which selectively inhibits lysis of SRBC, ER-specific monoclonal antibody and simple sugars decrease cytolysis against all target cells tested.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002417:Cattle; D002645:Chickens; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008358:Mannose / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D012397:Rosette Formation; D012756:Sheep; D014357:Trypsin
D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014357:Trypsin; D008358:Mannose