T CELL CONTROL OF AUTOREACTIVITY IN MURINE SLE

尽管T细胞密切参与肿瘤的发生和发展 小鼠系统性红斑狼疮(SLE)的认识 它们在疾病中的作用一直难以捉摸。我们之前对T-的研究 细胞对Sm核抗原的反应性提供了一种系统 探讨T细胞对系统性红斑狼疮中一种重要抗原的识别作用。 我们将定义Sm反应性T细胞所利用的T细胞受体 通过建立对小鼠Sm有反应的T细胞杂交瘤，鉴定 T细胞受体V基因家族，并对这些基因进行测序 我们可以将杂交瘤相互比较，然后 生殖系遗传因素。 LPR是一个单一的隐性基因，导致一个基因的大量扩张 人L3T4-LYT-2-(“双阴性”)T淋巴细胞亚群 外围。我们希望了解这些T细胞是如何激发 自身免疫性疾病，因此将探索它们的起源和 通过采用迁移实验获得的分化能力 用Ly-1同源Lpr小鼠。我们将进一步定义这种疾病-- 应用单抗进行相关双阴性血统分析 针对胸腺双阴性细胞。我们会调查的 鸡传染性支气管炎杂交瘤细胞的表面受体及其功能 LPR双阴性细胞以了解这些细胞 在克隆水平上。通过LPR和Normal的收养转移 骨髓进入双重杂合子LPR宿主，我们会问 突出的B细胞和巨噬细胞异常特征 是由于异常的T细胞或 而是反映了其他骨髓的内在异常 派生的血统。最后，我们将利用LPR的能力来 在不同背景的小鼠上诱导自身免疫以确定 主要组织相容性I类和II类的影响 系统性红斑狼疮相关基因的表达。

Although T cells are intimately involved in the development of murine systemic lupus erythematosus (SLE), the understanding of their role in disease has been elusive. Our previous studies of T- cell reactivity to the Sm nuclear antigen have provided a system to investigate T-cell recognition of an antigen important in SLE. we will define the T-cell receptors utilized by Sm-reactive T cells by creating T-cell hybridomas reactive to mouse Sm, identifying the T-cell receptor V gene families, and sequencing the genes so that we can compare the hybridomas to each other and to germline genetic elements. Lpr is a single recessive gene which causes vast expansion of a population of L3T4- LYT-2- ("double negative") T lymphocytes in the periphery. We wish to understand how these T cells provoke autoimmune disease and thus will explore their origin and differentiative capacity through adoptive transfer experiments using Ly 1 congenic lpr mice. We will further define this disease- related double negative lineage using monoclonal antibodies directed against thymic double negative cells. We will investigate the surface receptors and function of hybridomas generated from the lpr double negative cells to gain understanding of these cells at the clonal level. By adoptive transfer of lpr and normal marrow into doubly heterozygous lpr hosts, we will ask whether the prominent B cell and macrophage abnormalities characteristic of lpr mice are due to the action of the abnormal T cells or instead reflect intrinsic abnormalities in other bone marrow derived lineages. Finally, we will exploit the capacity of lpr to induce autoimmunity on diverse murine backgrounds to determine the influence of major histocompatibility class I and class II genes on expression of SLE.