ZN STATUS AND T CELL DISORDER

描述（改编自研究者摘要）：既往研究 申请人已经证明，在没有低锌血症的情况下， 当锌缺乏只是轻微或 边缘。在这些病例中，锌缺乏的诊断是基于 淋巴细胞、粒细胞和血小板中的锌水平降低。 由于金属硫蛋白-2（肝MT）的mRNA在肝细胞中表达， 锌的调节控制，血浆中MT-2和锌的测定可 提供了一个简单而准确的锌状态评估。 申请人 已经从人肝脏中产生了抗MT-2的单克隆抗体， 成功地建立了人血浆中MT-2的放射免疫测定法。 有了这项技术，将有可能评估锌状态， 实验人类模型受试者，其中轻度缺锌将 通过饮食方式诱导，并将血浆MT-2水平与细胞凋亡相关。 锌和基线期间淋巴细胞外5'核苷酸酶活性 限制和锌充满阶段。 此外，使用70 Zn， 活动体锌池测量将用于进一步确定 在基线期间实验人类模型受试者中锌的状态， 锌限制和锌充满阶段。如果这些研究表明， 血浆MT-2和锌的测定真实地反映了 人类，诊断程序可以简化，以制定一个 用于MT-2测定的商业放射免疫测定试剂盒。 锌是一种重要的 在人类和实验动物的免疫功能中的作用。 Inasmuch 由于锌的微量缺乏可能在全世界普遍存在， 拟议的研究将提供评估锌状况的技术， 将其与常见的各种免疫功能障碍联系起来， 人类缺锌的情况下，并提供锌的作用机制， 细胞介导的免疫功能。 先前在实验人类中的研究 模型受试者显示，血清中的活性胸腺肽和IL-2 单核细胞的生产受到影响的早期，而损害 IL-1的产生和NK细胞的活性在锌的作用时间较晚 限制期。 申请方还观察到淋巴细胞减少 胞外5'核苷酸酶活性（被认为是细胞增殖的酶标志物） 在锌限制阶段早期成熟。申请人建议 研究轻度缺锌可能导致 IL-1产生、IL-2产生和NK细胞活性受损：1） 减少相关细胞的比例，2）抑制 - 相关细胞的功能活性，通过拟南芥素和/或TGFB， 和3）相关功能活动的内在缺陷 细胞

DESCRIPTION (Adapted from Investigator's Abstract): Previous studies by the applicant have shown that in the absence of hypozincemia there may be adverse immunological effects when the deficiency of zinc is only mild or marginal. In these cases, the diagnosis of zinc deficiency was based on decreased levels of zinc in lymphocytes, granulocytes, and platelets. Inasmuch as the mRNA of metallothionein-2 (liver MT) is under the regulatory control of zinc, the assay of MT-2 and zinc in the plasma may provide a simple and accurate assessment of zinc status. The applicant has produced a monoclonal antibody to MT-2 from human liver and has succeeded in setting up a radio-immune assay for MT-2 in human plasma. With this technique, it will be possible to assess zinc status in experimental human model subjects, in whom a mild deficiency of zinc will be induced by dietary means and correlate plasma MT-2 levels with cellular zinc, and lymphocyte ecto 5' nucleotidase activity during baseline, zinc restricted, and zinc repleted phases. Additionally with the use of 70Zn, mobilizable body zinc pool measurement will be used to further define the status of zinc in the experimental human model subjects during baseline, zinc restricted, and zinc repleted phases. If these studies show that measurement of MT-2 and zinc in plasma truly reflected zinc status in humans, the diagnostic procedures can be simplified to develop a commercial radio-immune assay kit for MT-2 assay. Zinc plays an important role in immune functions in both man and experimental animals. Inasmuch as a marginal deficiency of zinc may be prevalent throughout the world, the proposed studies will provide techniques for assessing zinc status and relate this to various immunological dysfunctions commonly observed in cases of human zinc deficiency and provide mechanisms of zinc action on cell mediated immune functions. Previous studies in experimental human model subjects have shown that active thymulin peptide in serum and IL-2 production by mononuclear cells are affected early, whereas impairment of IL-1 production and NK cell activity appears later during the zinc restricted period. The applicant has also observed decreased lymphocyte ecto 5' nucleotidase activity (believed to be an enzymatic marker of cell maturity) early during the zinc restricted phase. The applicant proposes to investigate three mechanisms by which mild zinc deficiency could cause impaired IL-1 production, IL-2 production and NK cell activity: 1) reductions in the proportions of the relevant cells, 2) suppression of the functional activity of the relevant cells by prostaglandins and/or TGFB, and 3) intrinsic defects in the functional activities of the relevant cells.