ZN STATUS AND T CELL DISORDER

描述(改编自调查人员摘要)：之前的研究 申请人已经证明，在没有低锌血症的情况下，可能有 仅轻度缺锌或缺锌时的免疫不良反应 边缘。在这些病例中，缺锌的诊断是基于 降低淋巴细胞、粒细胞和血小板中的锌水平。 由于金属硫蛋白-2(肝脏MT)的信使核糖核酸(MMT) 锌的调控，血浆中MT-2和锌的测定可 提供简单而准确的锌状态评估。申请人 已经从人类肝脏中产生了一种抗MT-2的单抗，并已经 成功地建立了人血浆中MT-2的放射免疫分析方法。 有了这项技术，将有可能评估锌的状态 实验人体模型受试者，在其中轻度缺锌 饮食诱导及血浆MT-2水平与细胞 与基线期间淋巴细胞胞外5‘核苷酸酶活性 受限相和锌再镀相。此外，由于使用了70Zn， 将使用可移动身体锌池测量来进一步定义 实验人体模型受试者在基线期间锌的状况， 锌的限制相和锌的复制相。如果这些研究表明 血浆MT-2和锌的测定真实地反映了儿童的锌状况 人类，可以简化诊断程序以开发出一种 用于MT-2检测的商用放射免疫分析试剂盒。锌扮演着重要的角色 在人和实验动物的免疫功能中的作用。鉴于此， 由于锌的边际缺乏可能在世界各地普遍存在， 拟议的研究将提供评估锌状况的技术和 这与各种免疫功能障碍有关，通常在 人体缺锌病例及锌作用机制的研究 细胞介导的免疫功能。先前在实验人体中的研究 模型受试者已显示血清中活性胸腺肽和IL-2 单个核细胞的产生会在早期受到影响，而 IL-1的产生和NK细胞的活性在补锌的后期出现 限制期。申请人还观察到淋巴细胞减少。 ECTO 5‘核苷酸酶活性(被认为是细胞的酶标记 在锌限制阶段的早期)。申请人提出建议 研究轻度缺锌可能导致的三种机制 IL-1、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 前列腺素和/或转化生长因子b对相关细胞的功能活性， 3)相关机构的职能活动存在固有缺陷 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.