EXPERIMENTAL INDUCTION OF SLE BY ALTERED IA

描述：(改编自申请者的摘要)-慢性GVH 在近交系小鼠中通过移植脾和 识别外源MHC II类决定簇的淋巴T细胞 收件人。这种综合征的特征是一系列 自身抗体和免疫病理变化与这些密切相关 发现于人类系统性红斑狼疮。之前的工作，由 首席调查员的实验室和其他人已经表明， 疾病是由供体识别同种异体反应性T细胞引起的 受体B细胞上的外来MHC II类分子依次被诱导 以产生自身抗体。在当前应用程序中，主体 调查人员建议研究捐赠者的具体作用和 慢性移植物抗宿主病的受体T细胞和受体B细胞。他的 具体目标是(1)了解慢性粒细胞白血病患者B细胞耐受性是如何丧失的 GVH反应；(2)了解内源性T细胞在 慢性GVH反应；以及，(3)确定供体的作用是什么 慢性GVH反应中的T细胞。申请者期望这些研究， 将对自身抗体的机制提供重要的见解 慢性GVH反应中的产生和耐受性丧失。这个，他们 相信，将有助于理解产生 自发性系统性红斑狼疮的耐受性丧失特征 红斑狼疮(SLE)，无论是在小鼠身上还是在人类身上。这样的理解将， 最终，导致对这种疾病和其他疾病的更合理的治疗 自身免疫性疾病。

DESCRIPTION: (Adapted from the applicant's abstract) - The chronic GVH reaction is induced in inbred strains of mice by a transfer of spleen and lymph node T cells that recognize a foreign MHC class II determinant in the recipient. This syndrome is characterized by a spectrum of autoantibodies and immunopathological changes that closely parallels those found in human systemic lupus erythematosus. Previous work by the principal investigator's laboratory and others have shown that this disease is induced by the donor alloreactive T cells that recognize foreign MHC class II on B cells of the recipient that are in turn, induced to produce autoantibodies. In the current application, the principal investigator proposes to study the specific role of the donor and recipient T cells as well as the recipient B cells in chronic GVH. His specific aims are (1) To learn how B cell tolerance is lost in the chronic GVH reaction; (2) to understand what the role is of endogenous T cells in the chronic GVH response; and, (3) to determine what the role is of donor T cells in the chronic GVH response. These studies, the applicants expect, will provide important insight into the mechanism of autoantibody production and loss of tolerance in the chronic GVH response. This, they believe, will help in understanding the underlying mechanisms that produce the loss of tolerance characteristic of spontaneous systemic lupus erythematosus (SLE), both in mice and in humans. Such understanding will, eventually, lead to more rational therapy for this disease and other autoimmune diseases.