Natural killer cell function in trisomy-21 (Down's syndrome)

Natural killer (NK) activity and antibody-dependent cell mediated cytotoxicity (ADCC) against a human myeloid target cell line (K 562) was measured in adult patients with trisomy-21 (Down's syndrome) and in chromosomally normal age and sex matched control subjects. The effect of human leucocyte interferon (IFN-alpha) on the NK activity was also estimated. Spontaneous NK activity was stronger in the adult patients with trisomy-21 than in the healthy controls, but the difference did not reach statistical significance. The augmentation of NK activity by IFN-alpha, measured using lymphocytes not depleted of monocytes as effector cells, was statistically significant in both the trisomic patients (P less than 0.004) and the healthy controls (P less than 0.0005). Using monocyte and macrophage depleted lymphocytes in the patients with trisomy-21 the NK activity proved stronger than in the healthy controls, but not significantly and IFN-alpha did not augment it as it did in the healthy controls (P = n.s., P less than 0.05), for augmentations respectively). These results support the view that monocytes and macrophages are connected with the NK cell system. ADCC correlated with NK activity in both groups. Since NK cells are important components of many immune processes, including tumour and virus and/or bacteria-infected cell elimination, and have regulatory functions in immune reactions, the deficient augmentation of trisomic NK cells shown in vitro with extrinsic human leucocyte interferon may, paradoxically be an explanation for the greater susceptibility of trisomic individuals to lymphatic leukaemia and virus and bacterial infections. In vivo, this could be explained by the more potent secondary suppression by the 'immune' interferon produced by the virus, bacteria and malignant cells. In other words, the potential of the 'fighting couple' of the immune system, NK cell/interferon, is perhaps disturbed genetically due to the chromosome 21.