REGULATORY T CELLS

已经描述了几个模型系统，其中T细胞反应 抗原本身可以通过一秒钟的时间激发抑制性免疫反应 限制对这些抗原的进一步反应的T细胞群。T 对MHC抗原有反应的细胞会诱导深刻而特异的 对GVH疾病的抵抗力；T细胞对脑源性反应 髓鞘碱性蛋白的片段，这通常会导致瘫痪的EAE， 诱导对EAE的抵抗；一些研究表明，在体内 对超级抗原的反应，涉及急剧增加和减少 在选定的V-βT细胞群中，不能重新诱导；还有 证明TCR多肽免疫可激发一种免疫 抑制表达所选TCR的T细胞功能的反应 分子。虽然这些模型中的一些已经被更彻底地探索 在每一种情况下，TCR分子似乎都是克隆的 从它们衍生的特定多肽，诱导激活调节 T细胞对这些TCR标志物具有特异性。这种抗受体药物 免疫反应可能反映了一种潜在的自我耐受机制 外周T细胞库，用于限制对自身和 环境抗原，这可能是理性方法的基础 用于控制至少一些免疫疾病状态。 这项建议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行， 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TCRβ链 以及调节性T细胞是否在 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.