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.

Hirschsprung-associated enterocolitis develops independently of NOD2 variants

“…These include a deficient transfer of secretory IgA across enterocytes, a defective white cell function, and an impaired immune response [13]. The theory of an impaired immune response originates from the observation that HD is associated with a higher incidence of HAEC when combined with trisomy 21, as children with Down syndrome exhibit impaired humoral as well as cellular immune functions [22,23]. In the current study, we excluded syndromic cases of HD.…”

Cell-mediated cytotoxicity in down syndrome: impairment of allogeneic mixed lymphocyte reaction, NK and NK-like activities

“…Some evidence suggests that NK-like activity is mediated by MLC-induced T cells [40], or that NK-like activity is mediated by a subpopulation of circulating NK cells [50,56]. In fact, it is well known that the IFRec gene, coding for the species-specific response to interferon, is localized on the human chromosome 21 and that trisomic cells including fibroblasts, monocytes, lymphocytes and NK cells have enhanced sensitivity to the effect of interferon [12,14,18,41,43,44,53,59,60,63]. One explanation is that NK activity is low in DS because the majority of NK cells are immature (HNK -1+, CD 3 + ).…”

New insights into the pathogenesis of Hirschsprung’s associated enterocolitis

“…The combination of HD and trisomy 21 is associated with a higher incidence of enterocolitis with 50% of patients with Trisomy 21 and HD developing into HAEC as opposed to 29% in the normal population [2]. Infants with Trisomy 21 have an intrinsic immunity deficiency due to both decreased cytotoxic Tlymphocytes and derangement in humoral function which may explain their increased risk of developing HAEC [52][53][54].…”