Abnormal natural killer cell activity in systemic lupus erythematosus: an intrinsic defect in the lytic event

The natural killer (NK) cell activity in fifteen systemic lupus erythematosus (SLE) patients was investigated by employing 51-chromium- (51Cr) release microcytotoxicity and single cell cytotoxicity assays against K562 target cells. Although the SLE patients as a group had depressed NK function in the 51Cr-release assay compared to normal subjects (p less than 0.005), those with clinically active disease displayed the greatest impairment in this activity (p less than 0.001). Active SLE patients were deficient in overall NK activity (Vmax) (p less than 0.005) but had normal percentages of potentially cytotoxic target binding cells (TBC). These TBC, however, were unable to normally kill bound target cells (p less than 0.01), which is indicative of a deficiency of "active" NK cells (p less than 0.005). Those NK cells with intact cytotoxic capabilities could "recycle" and repeat the lytic sequence normally. Exposure of normal lymphocytes to SLE sera did not impair any phase of NK function. These studies indicate that defective NK activity in SLE is secondary to an abnormality in the lytic event itself and is not due to a deficiency of NK cells, an abnormality in target binding, or an inability of NK cells to lyse multiple targets. Additionally, serum factors do not appear to play a major etiologic role in the cytotoxic abnormalities of these patients.