LYMPHOCYTES AND HISTOCOMPATIBILITY ANTIGENS

本建议侧重于以下三个方面的相互作用： T淋巴细胞和MHC基因产物：（i） 特异性诱导的对GVH疾病的抗性，（ii）细胞免疫应答， 自身免疫性疾病的诱导和发病机制 在接受长期治疗的大鼠中， 环孢菌素A，和（iii）是否共同的机制， 涉及MHC特异性T细胞的独特型-抗独特型相互作用 而受体特异性调节T细胞是这两种疾病的基础 模型 此前由该补助金支持的研究表明， 同种异体反应性亲本株（A）T细胞携带相关标志物 其行为类似于高度保守的抗MHCb独特型 受体。 作为成年A/B F1大鼠的免疫原，它诱导了一种免疫应答。 延长的特异性T细胞介导的对GVH的抵抗状态 由任何来源的抗MHCb T细胞引起的疾病。 作为 在新生A/B F大鼠中， 对由抗b T细胞引起的GVH疾病的特异性敏感性。 的 应答的F1 T细胞包括抑制 同种异体反应性-在体内，并在体外对MLC母细胞裂解。 在 在这两种情况下，这些“调节性抗独特型T细胞不会出现 是MHC限制型的 要进行的研究旨在探索 自身反应性T细胞（例如B抗B）具有相同的独特型 在同种异体反应性（A抗b）T细胞上发现的标记物， 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， 保持自身的耐受性。

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.