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IMMUNOTOXIC EFFECTS OF IODINE

碘的免疫毒性作用

基本信息

批准号：
6177355
负责人：
Carol Lynne Burek
金额：
$ 20.44万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-04-01 至 2002-03-31
项目状态：
已结题

项目摘要

DESCRIPTION: (Adapted from the investigator's Abstract) Autoimmune thyroiditis is a multifactorial condition with several genetic and environmental components contributing to disease. Iodine has been implicated as one of these components. The broad long-term objectives remain to explore the immunotoxic of iodine in autoimmune thyroiditis (AT). Increased environmental exposure to iodine from dietary or therapeutic sources may contribute to the increasing prevalence of AT in humans. Both animal models of thyroiditis and clinical observations in humans relate ingestion of excess iodine as a potent risk factor in subjects genetically predisposed to AT. However, the pathogenic mechanism has not been determined. The investigator's hypothesis is that excess ingested iodine leads to highly iodinated Tg, and that the highly iodinated Tg is a more potent auto-immunogen than poorly-iodinated Tg in subjects predisposed to AT. As a new direction from their current research on humans, they will use a mouse model as the primary test system to study the role of iodine in triggering the expression of AT. The congenic mutant strain of NOD mice (NOD.B10.A (4R)-H2-H4) do not get diabetes but do get thyroiditis that is exacerbated by dietary iodine. The investigator will continue to study the role of iodinated Tg in humans using in vitro cell techniques. The specific aims for this proposal are: 1. To show that ingested iodine promotes AT in the NOD mouse model and establish basic and immunological parameters. The investigator will study the effect of iodine dose, timing, age, sex, on disease induction, on phenotype of cells in the thyroid. He will determine the frequency of these cells and then relate these findings to their cytokine and antibody profiles. 2. To induce thyroiditis in vivo. He will show that T cells from mice with lesions after a high iodine diet will transfer disease into non-affect recipients, first, with spleen cells from iodine-treated mice, then iodinated Tg to support the hypothesis. Individual parameters of the immune system will be monitored as for specifics aim 1. 3. To show in human studies that T cell clones preferentially recognize highly iodinated Tg greater than poorly iodinated Tg, to establish frequency of these cells by limiting dilution and determine their cytokine profiles in order to relate these findings to disease. The mouse model permits mechanistic research of dietary iodine that is closely analogous to humans and allows experimental procedures that cannot be done in humans. If the mechanism of disease can be clarified, then the potential exists for developing strategies to abrogate the deleterious immune response.

描述：（改编自研究者摘要）自身免疫性甲状腺炎是一种多因素疾病，具有多种遗传性和导致疾病的环境因素。碘已经作为其中的一个组成部分。广泛的长期目标碘对自身免疫性甲状腺炎（AT）的免疫毒性仍有待进一步研究。通过饮食或治疗增加环境中碘暴露来源可能导致AT在人类中的患病率增加。两甲状腺炎的动物模型和人类临床观察相关摄入过量碘是受试者遗传学上的潜在风险因素易患AT 然而，其致病机制尚未完全阐明，测定研究者的假设是过量摄入的碘导致高度碘化的Tg，并且高度碘化的Tg是更高的碘化Tg。在易患以下疾病的受试者中，原子作为他们目前对人类研究的新方向，他们将使用小鼠模型作为研究碘在触发AT的表达。 NOD小鼠的同源突变株（NOD.B10.A（4 R）-H2-H4）不会得糖尿病，但会得甲状腺炎，因碘摄入而恶化研究者将继续研究使用体外细胞技术研究碘化Tg在人体中的作用。具体这项建议的目的是：1。为了证明摄入的碘促进AT，建立NOD小鼠模型，并建立基础和免疫学参数。的研究者将研究碘剂量、时间、年龄、性别对疾病诱导，对甲状腺细胞表型的影响。他将决定这些细胞的频率，然后将这些发现与它们的细胞因子和抗体谱。 2. 在体内诱发甲状腺炎。他将表明高碘饮食后有病变的小鼠的T细胞将将疾病转移到非受影响的受体中，首先，碘处理的小鼠，然后碘化Tg以支持该假设。将监测免疫系统的个体参数，具体目标1. 3. 在人体研究中显示T细胞克隆优先识别高碘化Tg大于低碘化Tg Tg，通过有限稀释确定这些细胞的频率，并确定他们的细胞因子谱，以便将这些发现与疾病联系起来。的小鼠模型允许膳食碘的机制研究，类似于人类，并允许实验程序，在人类身上。如果疾病的机制能够被阐明，那么潜在的存在于发展消除有害免疫的策略中反应