Association of decreased T-cell-mediated natural cytotoxicity and interferon production in Down's Syndrome

Abstract

Total peripheral blood lymphocytes (PBL) and isolated subpopulations from children with Down's Syndrome (DS) and age-matched healthy controls were investigated for their (1) natural killer (NK) and antibody-dependent cellular cytotoxic activities, (2) interleukin 2 (IL-2)-induced augmentation of NK activity, (3) lectin-dependent cellular cytotoxicity (LDCC), (4) ability of serum- and culture-derived soluble suppressor factor(s) to inhibit NK activity of normal lymphocytes, and (5) capacity to produce interferon (IFN) against tumor targets in vitro. T lymphocytes from DS patients demonstrated significantly decreased NK activity against K562 target cells compared to controls. DS lymphocytes also demonstrated a significant reduction in LDCC activity and IL-2-induced enhancement of NK activity. Furthermore, the ability of DS lymphocytes to produce IFN in vitro against K562 target cells was also significantly lower than that for normal PBL. Although sera from DS patients showed a significantly greater inhibitory effect on the NK activity of allogeneic normal PBL than normal sera, culture supernates from DS lymphocytes demonstrated suppressive effects comparable to culture supernates from normal PBL. These studies suggest an association between the decreased NK activity of T-cell subpopulations and lower IFN production by PBL from patients with DS.