LYMPHOCYTES AND HISTOCOMPATIBILITY ANTIGENS

这一建议侧重于以下三个方面的互动： T淋巴细胞与MHC基因产物：(一)细胞基础 特异性诱导对GVH病的抗性，(Ii)细胞 自身免疫性疾病的诱发和发病机制 在接受长疗程治疗的大鼠中， 环孢菌素A，以及(Iii)是否基于 MHC特异性T细胞的独特型-抗独特型相互作用 和受体特异性调节T细胞是这两种疾病的基础 模特们。 之前由这笔赠款支持的研究表明， 同种异体亲本株(A)T细胞携带相关标志 它的行为类似于高度保守的抗MHCb独特型 感受器。作为一种免疫原，在成年A/B F1大鼠体内诱导产生 延长的特异性T细胞介导的GVH抵抗状态 由任何来源的抗MHCb T细胞引起的疾病。作为一名 新生A/B/F大鼠的耐受性它诱导了一种精致和 对抗b-T细胞引起的GVH疾病的特异性敏感性。这个 应答的F1 T细胞包括一个抑制 同种异体反应性-在体内，对MLC细胞在体外是溶解的。在……里面 在这两种情况下，这些“调节器”抗独特型T细胞都没有出现 将受到MHC的限制。 将要进行的研究旨在探索这种可能性 自身反应性T细胞(如B、抗-b)具有相同的独特型 在同种异体反应性(A抗b)T细胞上发现的标志物，以及 调节性、抗独特型T细胞控制这些基因的表达 独特型抗MHC T细胞作为正在进行的过程的一部分 在保持自我容忍方面。

This proposal focuses on three aspects of the interaction between T lymphocytes and MHC gene products: (i) the cellular basis of specifically induced resistance to GVH disease, (ii) the cellular mechanisms underlying the induction and onset of autoimmune disease in rats undergoing a prolonged course of treatment with cyclosporine A, and (iii) whether common mechanisms based on idiotype-anti-idiotype interactions involving MHC specific T cells and receptor specific regulator T cells underly these two disease models. Previous studies supported by this grant have shown that alloreactive parental strain (A) T cells carry associated marker which behaves like a highly conserved idiotype of anti-MHCb receptors. As an immunogen in adult A/B F1 rats it induces a prolonged and specific T cell mediated state of resistance to GVH disease caused by anti-MHCb T cells from any source. As a tolerogen in newborn A/B F rats it induces an exquisite and specific sensitivity to GVH disease caused by anti-b T cells. The responding F1 T cells include a subset which suppresses alloreactivity-in vivo and is lytic for MLC blasts in vitro. In both cases these "regulator anti-idiotypic T cells do not appear to be MHC restricted. The studies to be performed are designed to explore the possibility that autoreactive T cells (e.g. B anti-b) have the same idiotypic marker found on alloreactive (A anti-b) T cells, and that regulatory, anti-idiotypic T cells control the expression of these idiotypic anti-MHC T cells as part of the ongoing process involved in the maintenance of self tolerance.