CHARACTERIZATION OF THE IMMUNOREGULATORY CIRCUITS IN MAN

人类免疫调节回路的特征

• 批准号: 3156626
• 负责人: Chikao Morimoto
• 金额: $ 19.37万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156626
• 关键词: Sjogren's syndrome; autoimmune disorder; cell cell interaction; clone cells; helper T lymphocyte; human subject; immunodeficiency; immunopathology; immunoregulation; immunotherapy; juvenile rheumatoid arthritis; membrane activity; monoclonal antibody; suppressor T lymphocyte; systemic lupus erythematosus

T lymphocytes play a central role in the immune response by specifically recognizing antigens and functioning as effector or regulatory cells. Major recent technical breakthroughs in the molecular characterization of T lymphocyte subsets, and in identification of lymphokines responsible for lymphocyte activation should facilitate the development of important new insights into the immunoregulatory circuits in man. Our long-term objective is directed at defining the structural basis of characterization of the regulatory circuits involved in the generation of both help and suppression in man using a combination of molecular biology, biochemistry and cellular immunology. This information will provide important insights into the nature of molecular and cellular defects seen in autoimmune diseases such as SLE and RA. The specific aims of this proposal are: 1) Activation mechanisms employed by subsets of T4 cells will be studied. Cell surface molecules involved in activation of T4+2H4+ suppressor inducer and T4+4B4+ helper inducer cells will be characterized. Moreover, the spectrum of lymphokines such as IL-2, IL-3, IL-4, IL-5, etc., produced by subsets of T4 cells will be studied. 2) The mechanism by which activated suppressor inducer cells interact with T8 suppressor cells to generate suppressor signals will be studied. The cell surface molecules on activated T4+2H4+ cells or of the recently developed T4+2H4+ suppressor inducer cell line that participate in suppressor cell activation will be studied. We also plan to develop new monoclonal antibodies against the T4+2H4+ suppressor inducer cell line to characterize the antigen recognition unit and to identify new cell surface molecules involved in suppressor inducer function. These antibodies will be used to study the structural basis of suppressor signals in T4+2H4+ suppressor inducer cells. 3) The molecular and cellular basis of defective regulatory circuits in patients with autoimmune diseases will be determined. Differences in the expression of 2H4 and new functional surface molecules, and LCA gene expression in SLE patients will be determined. Mechanisms of generating helper and suppressor signals in SLE patients will also be studied and the specificity of anti-T cell antibodies found in SLE plasma will be determined using transfected target cells. The expression of 4B4 and LCA molecules at both protein and genomic levels in synovial lymphocytes from patients with RA, etc., will also be determined.

T淋巴细胞在免疫应答中发挥核心作用， 特异性识别抗原并作为效应物或 调节细胞 最近的重大技术突破， T淋巴细胞亚群的分子特征， 鉴定负责淋巴细胞活化的淋巴因子 应该有助于发展重要的新见解， 人类的免疫调节回路。我们的长期目标是 旨在确定表征的结构基础， 参与生成帮助和 使用分子生物学， 生物化学和细胞免疫学。 这些信息将 提供了重要的见解的性质，分子和 在自身免疫性疾病如SLE和RA中观察到的细胞缺陷。 本建议的具体目标是：1）激活机制 将研究T4细胞亚群所采用的方法。 细胞表面 参与激活T4+ 2 H4+抑制诱导物的分子， 将对T4+ 4 B4+辅助诱导细胞进行表征。 而且 淋巴因子谱，如IL-2、IL-3、IL-4、IL-5等， 将研究由T4细胞亚群产生的细胞。 2)机制 通过激活的抑制诱导细胞与T8相互作用 将研究产生抑制信号的抑制细胞。 活化的T4+ 2 H4+细胞上的细胞表面分子或 最近开发的T4+ 2 H4+抑制诱导细胞系， 参与抑制细胞激活的研究。 我们也 计划开发针对T4+ 2 H4+的新单克隆抗体 抑制诱导细胞系以表征抗原 识别单位和识别新的细胞表面分子 参与抑制诱导物功能。 这些抗体将 用于研究T4+ 2 H4+中抑制信号的结构基础 抑制诱导细胞 3)的分子和细胞基 自身免疫性疾病患者的调节回路缺陷 将被确定。 2 H4和新基因表达的差异 功能性表面分子和LCA基因在SLE中的表达 患者将被确定。 产生辅助细胞的机制， SLE患者中的抑制信号也将被研究， 在SLE血浆中发现的抗T细胞抗体的特异性将是 使用转染的靶细胞测定。 4 B4的表达 和LCA分子在蛋白质和基因组水平在滑膜中的表达。 来自RA患者的淋巴细胞等，也将被确定。