Natural cytotoxicity in systemic lupus erythematosus: mechanisms of suppression by inhibitory serum factors

Abstract

Spontaneous cytotoxicity mediated by natural killer (NK) cells is impaired in several human diseases including systemic lupus erythematosus (SLE). The present study was designed to describe factors in SLE sera which suppress the NK function of unfractionated mononuclear cells and NK enriched suspensions. NK activity was determined in 19 SLE patients and 25 normal controls by a standard chromium release assay. Sera obtained from SLE patients suppressed normal NK activity by an average of 29.4%. The presence of anti-lymphocyte antibodies (ALA) of the IgM class which were reactive with unfractionated mononuclear cells or the NK cell enriched OKM1 positive subset correlated with serum-mediated suppression. NK inhibitory SLE sera did not interfere with normal effector-target conjugate formation. These results demonstrate the modulatory effects of immune aggregates and ALA on lymphocyte function in SLE. These factors suppress NK function without evidence of lymphocyte cell death or inhibition of NK effector cell binding to tumour targets.