Deficiency of active natural killer cells in the Chediak-Higashi syndrome. Localization of the defect using a single cell cytotoxicity assay.

This study investigated the defective natural killer (NK) cell activity in two patients with the Chediak-Higashi syndrome (CHS) using both a standard 51-chromium release microcytoxicity and a single cell-in-agarose assay against K562 and Molt-4 target cells. CHS patients were deficient in overall maximum NK capacity, but had normal percentages of potentially cytotoxic target bindng cells. the relative number of TBC that could kill bound targets (i.e., "active" NK cells) was significantly depressed in CHS patients when compared with normal controls. The diminished CHS active NK cells that were present, however, were capable of recycling and lysing multiple target cells during the assay period. In vitro interferon (INF) treatment of normal and CHS effector cells did not alter target cell binding, but did increase the maximum NK capacity, percentage of active NK cells and the maximum recycling capacity, as well as the rate of lysis. These studies indicate that the depression of NK activity in patients with CHS is secondary to a deficiency of active NK cells. The CHS active NK cells that are present, however, are capable of normal target lysis and recycling. Potentially cytotoxic pre-NK cells, which can bind but not kill target cells, can be activated by in vitro IFN to develop lytic activity. Thus, IFN treatment may be of potential benefit to the immune surveillance network of CHS patients by activating a population of pre-NK cells to express their cytotoxic potential.