Prasad A S
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.
Mol Cell Biochem. 1998 Nov;188(1-2):63-9.
Nutritional deficiency of zinc is widespread throughout the developing countries and a conditioned deficiency of zinc is known to occur in many diseased states. Zinc is known to play an important role in the immune system and zinc deficient subjects may experience increased susceptibility to a variety of pathogens. We have studied the effects of a mild deficiency of zinc on T cells in an experimental model of human zinc deficiency. We showed that T cell functions were affected adversely even when the deficiency of zinc was mild in humans. Characteristically during zinc deficiency, the serum thymulin activity (a thymic hormone) was decreased which was restored following zinc supplementation. Our studies also showed that zinc deficiency caused an imbalance between TH1 and TH2 functions. The production of IFN-g, IL-2, TNF-a (products of TH1 cells) were decreased, whereas the production of IL-4, IL-6 and IL-10 (products of TH2) were not affected during zinc deficiency. T cell subpopulation studies revealed that the CD4+ CD45RA+ to CD4+ CD45RO+ ratio was decreased as a result of zinc deficiency, suggesting that zinc may be required for the regeneration of new CD4+ T cells. We further documented that zinc deficiency decreased NK cell lytic activity and caused a decrease in the percentage of CD8+ CD73+ T cells which are known to be predominantly precursors of cytotoxic T cells. In a suitable cell culture model our studies revealed that the gene expression of a DNA synthesizing enzyme TK was affected adversely which resulted in delayed cell cycle and decreased cell growth. The above immunological consequences of zinc deficiency may be responsible for decreased cell mediated immune functions in zinc deficient subjects.
锌的营养缺乏在发展中国家普遍存在,而且已知在许多疾病状态下会出现锌的条件性缺乏。锌在免疫系统中发挥重要作用,锌缺乏的个体可能对多种病原体的易感性增加。我们在人类锌缺乏的实验模型中研究了轻度锌缺乏对T细胞的影响。我们发现,即使在人类轻度锌缺乏时,T细胞功能也会受到不利影响。锌缺乏时的特征是血清胸腺素活性(一种胸腺激素)降低,补充锌后可恢复。我们的研究还表明,锌缺乏导致TH1和TH2功能失衡。IFN-γ、IL-2、TNF-α(TH1细胞产物)的产生减少,而IL-4、IL-6和IL-10(TH2产物)的产生在锌缺乏时不受影响。T细胞亚群研究显示,由于锌缺乏,CD4+ CD45RA+与CD4+ CD45RO+的比例降低,这表明锌可能是新的CD4+ T细胞再生所必需的。我们进一步证明,锌缺乏会降低NK细胞的裂解活性,并导致CD8+ CD73+ T细胞百分比降低,已知这些细胞主要是细胞毒性T细胞的前体。在合适的细胞培养模型中,我们的研究表明,DNA合成酶TK的基因表达受到不利影响,导致细胞周期延迟和细胞生长减少。锌缺乏的上述免疫后果可能是锌缺乏个体细胞介导免疫功能降低的原因。