CHARACTERIZATION OF THE IMMUNOREGULATORY CIRCUITS IN MAN

T淋巴细胞在免疫反应中发挥着核心作用 特异性识别抗原并充当效应器或 调节细胞。 近期重大技术突破 T 淋巴细胞亚群的分子特征，以及 鉴定负责淋巴细胞活化的淋巴因子 应促进重要的新见解的发展 人体的免疫调节回路。 我们的长期目标是 旨在定义表征的结构基础 参与生成帮助和的调节电路 结合分子生物学对人类进行抑制， 生物化学和细胞免疫学。 该信息将 为分子和分子的本质提供了重要的见解 自身免疫性疾病（如 SLE 和 RA）中出现的细胞缺陷。 该提案的具体目标是： 1）激活机制 将研究 T4 细胞亚群所使用的。 细胞表面 参与 T4 2H4 抑制诱导剂激活的分子 T4 4B4 辅助诱导细胞将被表征。 此外， 淋巴因子谱，如 IL-2、IL-3、IL-4、IL-5 等， 将研究 T4 细胞亚群产生的。 2）机制 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 2H4 细胞或 最近开发的 T4 2H4 抑制诱导细胞系 参与抑制细胞激活将被研究。 我们也 计划开发针对T4 2H4的新单克隆抗体 抑制诱导细胞系来表征抗原 识别单元并识别新的细胞表面分子 参与抑制诱导功能。 这些抗体将 用于研究 T4 2H4 抑制信号的结构基础 抑制诱导细胞。 3）分子和细胞基础 自身免疫性疾病患者的调节回路有缺陷 将被确定。 2H4与new的表达差异 SLE 中的功能表面分子和 LCA 基因表达 患者将被确定。 生成helper的机制和 系统性红斑狼疮 (SLE) 患者的抑制信号也将得到研究， SLE 血浆中发现的抗 T 细胞抗体的特异性 使用转染的靶细胞确定。 4B4的表达 滑膜中蛋白质和基因组水平的 LCA 分子 RA等患者的淋巴细胞也将被测定。

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.