REGULATORY T CELLS

已经描述了几种模型系统，其中T细胞对免疫球蛋白具有反应性。 抗原本身可以在一秒钟内引发抑制性免疫反应， 限制对这些抗原的进一步反应的T细胞群。 不 对MHC抗原有反应的细胞将诱导一种深刻而特异的 对GVH疾病的抗性;对致脑炎性T细胞反应的T细胞 髓鞘碱性蛋白片段，通常引起麻痹性EAE， 诱导对EAE的抗性;一些研究表明， 对超级抗原的反应，包括急剧增加和减少 在选定的V-β T细胞群体中不能被重新诱导;也有 证明用TCR肽免疫引起免疫应答， 抑制表达选定TCR的T细胞功能的应答 分子。 虽然其中一些模型已经得到了更彻底的探讨， 在每种情况下，TCR分子或克隆 从它们衍生的特异性肽，诱导调节的激活， 对这些TCR标志物具有特异性的T细胞。 这种抗受体 免疫反应可能反映了自身耐受性的一种机制， 外周T细胞池用于限制对自身的应答， 环境抗原，它可能是合理的方法的基础， 来控制至少一些免疫疾病状态。 该提案概述了一系列旨在获得更好的 了解这些调节细胞的免疫生物学;是否 这些免疫抵抗模型通过一种共同的机制运作， 子集要求用于诱导和执行抗受体 免疫，免疫调节的目标是否与 TCR分子;调节性T细胞的TCR β链库 就像，调节T细胞是否在免疫系统中起调节作用， 胸腺

Several model systems have been described where T cells reactive to an antigen can themselves provoke suppressive immune responses by a second population of T cells that limit further responses to these antigens. T cells reactive to MHC antigens will induce a profound and specific resistance to GVH disease; T cells reactive to the encephalitogenic fragment of myelin basic protein, which usually cause paralytic EAE, induce resistance to EAE; some studies have indicated that in vivo responses to super antigens, involving dramatic increases and decreases in selected V-beta T cell populations cannot be reinduced; there are also demonstrations that immunization with TCR peptides provokes an immune response that inhibits function of T cells expressing selected TCR molecules. While some of these models have been more thoroughly explored than others, in each case, it appears that TCR molecules, or clonally specific peptides derived from them, induce the activation of regulatory T cells having specificity for these TCR markers. Such anti-receptor immune responses may reflect one mechanism underlying self tolerance in the peripheral T cell pool for limiting responses to self and environmental antigens, and it may be the basis of rational approaches for controlling at least some immune disease states. This proposal outlines a series of studies designed to acquire a better understanding of the immunobiology of these regulatory cells; whether these immune resistance models operate by a common mechanism, what the subset requirements are for inducing and executing anti-receptor immunities, whether the targets of immune regulation are associated with TCR molecules; what the TCR beta chain repertoire of regulatory T cells is like, and whether regulator T cells have a regulatory role in the thymus.