Nature of natural killer cell hyporesponsiveness in the Chediak-Higashi syndrome

Two unrelated Chediak-Higashi syndrome (CHS) patients in the prelymphomatous phase and their families were tissue typed and tested for their immune functions including natural killer cell (NK) activity. NK activity was assessed by the conventional 4 hr chromium release assay and by a newly developed single cell liquid cytotoxic assay (SLA). SLA permits the simultaneous study of the overall binding of peripheral blood mononuclear cells (PMNC) to the targets and the number of lytic conjugates. As expected, both CHS patients had low NK activity although their family members, including an HLA-identical sibling, were well within normal range. When tested with SLA, the percent total binding of the patient's PMNC was normal, but the number of lytic conjugates was lower than the normal controls. None of the patients had the A3,B7 haplotype which had been previously implicated in NK-hyporesponsiveness. T (including T helper and T suppressor cells) and B lymphocyte functions were normal (as assessed by mitogen stimulation, mixed lymphocyte reaction, and immunoglobulin synthesis). Our results suggest that CHS: (1) is not due to impaired target binding, and (2) is mainly due to low lytic efficiency of mature NK cells.