T-CELL CONTROL OF AUTOREACTIVITY IN SLE

T 细胞对 SLE 自身反应性的控制

• 批准号: 2848960
• 负责人: PHILIP L COHEN
• 金额: $ 27.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2848960
• 关键词: MHC class II antigen; T cell receptor; T lymphocyte; antigen antibody reaction; autoantibody; clone cells; cytokine; genetically modified animals; immunopathology; laboratory mouse; lymphocyte proliferation; systemic lupus erythematosus; tissue /cell culture; transfection

DESCRIPTION: (Adapted from the applicant's abstract) - T cells regulate the production of anti-Sm and other antinuclear antibodies in autoimmune mice. In this competitive renewal, a series of recently-derived Sm-specific CD4 T cell clones will be exploited in order to understand the specificity and function of T cells in this SLE model. Cytokine production, TCR gene usage, and specificity of the clones will be determined. Using TCR data from these clones, transgenic (tg) mice will be generated in which the T cell repertoire is skewed toward Sm-recognition, and the principal investigator and his colleagues will examine the consequences of humoral anti-Sm production. The immunogenic or immunosuppressive effects of in vivo administration of immunodominant Sm peptides will be explored using Sm-reactive TCR and control MRL/lpr mice. To investigate processing of Sm by autoantigen-specific B cells and its effect on the T cell repertoire, the repertoire and function of T cells from anti-Sm immunoglobulin tg mice will be examined. In additional experiments, taking advantage of recent data concerning peptides associated with MRL/lpr class II MHC molecules, evidence for autoreactivity against the antigens from which the peptides are derived will be sought, and it will be determined whether the autoimmune mice are tolerant to these antigens. Finally, unique anti-Sm transfected CH12 B lymphoma cells will be used as model APC to ask how Sm is processed, how it is presented to Sm-antigen specific T cells, and which APC are most efficient in Sm processing.

描述：（改编自申请人的摘要）- T细胞调节 自身免疫小鼠中抗Sm和其他抗核抗体的产生。在 这种竞争性更新，一系列最近衍生的Sm特异性CD 4 T细胞， 克隆将被利用，以了解特异性和功能， SLE模型中的T细胞。细胞因子产生、TCR基因使用和特异性 克隆人的数量将被确定。使用来自这些克隆的TCR数据， (tg)将产生其中T细胞库偏向于 SM识别，首席研究员和他的同事将检查 体液抗Sm产生的后果。免疫原性或 免疫显性Sm体内给药免疫抑制作用 将使用Sm-反应性TCR和对照MRL/lpr小鼠探索肽。到 自身抗原特异性B细胞对Sm加工及其影响 T细胞库，抗Sm抗体的T细胞库和功能 检查免疫球蛋白TG小鼠。在另外的实验中， 关于与MRL/lpr II类相关的肽的最新数据的优势 MHC分子，针对抗原的自身反应性的证据， 将寻求肽的来源，并将确定是否 自身免疫小鼠耐受这些抗原。最后，独特的抗Sm 转染的CH 12 B淋巴瘤细胞将被用作模型APC，以询问Sm是如何被激活的。 它是如何被呈递给Sm抗原特异性T细胞的，以及 在Sm处理中最有效。