Defective postbinding lysis underlies the impaired natural killer activity in factor vii-treated, human T lymphotropic virus type III seropositive hemophiliacs

We investigated the diminished natural killer (NK) activity in human T lymphotropic virus type III (HTLV-III) seropositive hemophiliacs. Despite normal percentages of NK cells, lymphocytes from five hemophiliacs showed impaired NK activity against K-562 tumor cells in 4-h chromium release microcytotoxicity assays. For example, at an effector-to-target cell ratio of 10:1, cells from patients caused 21.7 ± 2.5% lysis of tumor targets compared with 47.9 ± 5.1% lysis cells from controls (mean ± SEM, P < 0.005). Cells from patients were as cytotoxic in 18 h as were cells from controls in 4 h. Binding to tumor targets was not impaired since 11.0 ± 1.5% of cells from patients and 11.1 ± 1.3% of cells from controls bound to K-562 cells. Patient's binding cells, however, showed defective killing of attached tumor cells at all time points tested from 0 to 18 h. At 4 h, for example, patient's cells had lysed 10.9 ± 2.1% of attached tumor cells compared with 26.3 ± 3.3% lysis by controls' cells (P < 0.005). The percentage of lymphocytes which were active NK cells (i.e., cells that bound and lysed a tumor cell) was always lower for patients than for controls (1.17 ± 0.25% vs. 2.82 ± 0.33%, P < 0.005). Two methods for estimating recycling of effector cells against multiple target cells demonstrated that active NK cells from patients could recycle as well as those from controls (~3-4 times in 4 h). Mixing experiments showed no evidence for cellular suppression of NK activity. The lytic function of NK cells from HTLV-III seropositive hemophiliacs is thus heterogeneous. This is characterized by a defect in post-binding lysis, with relative sparing of binding capability and recycling capacity.