Deficiency of natural killer cell activity in patients with chronic lymphocytic leukemia

Abstract

Natural killer (NK)⁶ cell activity of peripheral blood lymphocytes against human leukemia cell lines was measured in patients with chronic B-cell lymphocytic leukemia (CLL) and age- and sex-matched controls. In order to remove the leukemia cells that interfere with the in vitro assay we (1) isolated lymphocytes that form rosettes with sheep red blood cells (SRBC) or (2) lysed the CLL cells with a monoclonal anti-B cell antibody and complement. NK activity in either lymphocyte preparation from nine of 10 patients with advanced disease was not detectable and, when calculated in terms of lytic units per ml of blood, was at least seven times lower than in controls; only one of these patients exhibited activity within the control range. Two patients with early disease had measurable, but low, NK-cell activity. Prolongation of the NK cell assay from 6 to 18h gave rise to significant killing in the CLL patients lacking NK cell activity in the 6-h assay; however, the activity still was six times lower than in controls. Treatment of leukemia cell-depleted lymphocytes from CLL patients with human fibroblast interferon or the interferon inducer poly I:C enhanced NK-cell activity in the two early stage patients but this treatment was ineffective in three later stage patients. The percentage of cells with characteristics of NK cells, i.e. those with receptors for SRBC and Fc-portion of IgG, was four times higher in CLL patients and the percentage of lymphocytes binding to NK-sensitive target cells was equal to that in controls despite the fact that, in the majority of patients, lysis of the target cells by the lymphocytes does not ensue. The NK deficiency may be responsible for the increased incidence of secondary malignancies in CLL patients.