CHARACTERIZATION OF THE IMMUNOREGULATORY CIRCUITS IN MAN

T淋巴细胞通过以下途径在免疫反应中发挥核心作用 特别是识别抗原并发挥效应器或 调节细胞。最近在技术上的重大突破 T淋巴细胞亚群的分子特征，以及在 淋巴细胞活化相关淋巴因子的鉴定 应促进发展对以下方面的重要新见解 人体内的免疫调节回路。我们的长期目标是 旨在定义表征的结构基础 HELP和HELP产生过程中涉及的调节回路 在人类中使用分子生物学的组合抑制， 生物化学和细胞免疫学。此信息将 提供对分子和分子的本质的重要见解 自身免疫性疾病中的细胞缺陷，如系统性红斑狼疮和类风湿性关节炎。 这项提议的具体目标是：1)激活机制 将研究T4细胞的子集所使用的。细胞表面 参与T4+2H4+抑制诱导物激活的分子和 将对T4+4B4+辅助诱导细胞进行鉴定。此外， IL-2、IL-3、IL-4、IL-5等淋巴因子的谱， 将研究由T4细胞亚群产生的。2)机制 激活的抑制子诱导细胞与T8相互作用 抑制细胞产生抑制信号将被研究。 活化的T4+2H4+细胞上的细胞表面分子 新近开发的T4+2H4+抑制诱导细胞系 参与抑制细胞的激活将被研究。我们也 计划开发新的抗T4+2H4+的单抗 用抑制子诱导细胞系鉴定抗原 识别单元并识别新的细胞表面分子 参与抑制诱导子功能。这些抗体将是 用于研究T4+2H4+中抑制信号的结构基础 抑制因子诱导细胞。3)分子和细胞基础 自身免疫性疾病患者的调节回路缺陷 将会被确定。2H4和new的表达差异 功能性表面分子与LCA基因在SLE中的表达 病人将会被决定。生成帮助器的机制和 SLE患者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 用转染靶细胞测定。4B4的表达 和LCA分子在滑膜中的蛋白质和基因组水平 类风湿性关节炎等患者的淋巴细胞也将被检测。

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.