ANTIBODY-DEPENDENT LYMPHOCYTE-MEDIATED GRANULOCYTE CYTOTOXICITY IN MAN

Abstract

Sera from 2 patients with granulocytopenia associated with collagen vascular disease caused the destruction of normal human granulocytes by autologous lymphocytes in vitro. Granulocyte cytotoxicity [GC], was measured by the release of 51Cr during incubation with test sera and lymphocytes in microtiter plates. Between 8 and 46% GC was produced in granulocytes from 8 normal donors by the sera from these 2 patients. Less than 6% GC was seen with the sera from 14 normal subjects and 29 patient controls. Treatment of lymphocyte preparations with carbonyl iron and magnetic separation to remove phagocytic cells, or treatment with complement[C]-coated red blood cells followed by repeated gradient centrifugation to remove C receptor-bearing lymphocytes, did not reduce the GC. There was a dose-response relationship between the concentration of positive sera and GC. When these sera were fractionated by Sephadex G-200 gel filtration and by ion-exchange chromatography with DEAE-cellulose, the active component appeared in the Ig[immunoglobulin]G-containing fractions. IgG antibody-dependent lymphocyte-mediated GC represents a means of detecting human granulocyte antibodies and is a possible mechanism of autoimmune neutropenia in these 2 patients.