Chédiak-Higashi gene in humans. II. The selectivity of the defect in natural-killer and antibody-dependent cell-mediated cytotoxicity function.
Antibody-dependent cell-mediated cytolysis (ADCC) of human tumor cells by FcR(+) nonadherent effector lymphocytes as well as natural killer (NK) activity was markedly impaired in Chediak-Steinbrinck-Higashi Syndrome (C-HS) patients. Compared to a more than 400-fold defect in NK activity in terms of lytic units, the abnormal ADCC response in C-HS donors was 24-fold below normal suggesting a partial but not complete overlap of lymphocytes or lytic mechanisms responsible for ADCC and NK. The ADCC mechanism against erythrocyte targets, however, was normal, thereby suggesting a qualitative difference in these two forms of ADCC. Other effector-cell functions against tumor-cell targets were normal as measured by (a) spontaneous cytolysis mediated by monocytes, (b) spontaneous cytostasis mediated by neutrophils, and (c) lectin-dependent cytolysis mediated by neutrophils. Although one C-HS patient was low in lectin-dependent cytolysis mediated by lymphocytes, the other C-HS patient was normal, thereby suggesting that cytolytic T function was not linked to the NK-ADCC defect. In addition, the proliferative response to T-dependent mitogens was also relatively normal. These results, combined with other studies showing normal cell-mediated and humoral immunity in these same patients, suggest that patients with C-HS have an immunodeficiency which is selective for NK and ADCC activity.
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D002478:Cells, Cultured; D002609:Chediak-Higashi Syndrome / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008934:Mitogens; D009000:Monocytes / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D008934:Mitogens