T CELL CONTROL OF AUTOREACTIVITY IN MURINE SLE

虽然T细胞密切参与了 小鼠系统性红斑狼疮（SLE），认识 它们在疾病中的作用是难以捉摸的。 我们以前对T- 细胞对Sm核抗原的反应性提供了一个系统 研究T细胞对SLE中重要抗原的识别。 我们将定义Sm反应性T细胞所利用的T细胞受体 通过产生与小鼠Sm反应的T细胞杂交瘤， T细胞受体V基因家族，并对基因进行测序， 我们可以将杂交瘤相互比较， 生殖系遗传因素 Lpr是一个单隐性基因， L3 T4- LYT-2-（“双阴性”）T淋巴细胞群体 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，因此将探索其起源， 通过过继转移实验的分化能力 使用Ly 1同源lpr小鼠。 我们将进一步定义这种疾病- 使用单克隆抗体的相关双阴性谱系 针对胸腺双阴性细胞。 我们将调查 产生的杂交瘤的表面受体和功能 lpr双阴性细胞来了解这些细胞 在克隆水平上。 通过lpr和正常的过继转移 骨髓双杂合lpr宿主，我们将问是否 显著B细胞和巨噬细胞异常特征 的lpr小鼠是由于异常T细胞的作用， 而是反映了其他骨髓中内在异常 衍生谱系。 最后，我们将利用lpr的能力， 在不同鼠背景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 基因对SLE表达的影响。

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.