HUMAN T CELL SUBSETS: ISOLATION AND CHARACTERIZATION

本提案的总体目标是针对孤立和 独一无二但仍未得到充分表征的亚群的特征 人类T淋巴细胞，认为这种细胞可能参与中枢 在向上和向下调节人类免疫反应的回路中。 其目的是利用最近在方法上的重大发展。 用于产生针对细胞表面抗原的抗体，用于 分离纯化的细胞亚群，用于克隆不同的 细胞群体，最后是功能的新方法 对这些细胞群体的分析。在目前的研究中，我们计划 对表型和功能特性进行详细分析 人类T淋巴细胞的独特亚群。特别是，我们计划 研制针对细胞表面分子的单抗探针，可以 将人类的诱导子和抑制子种群划分为不同的子集。 为了实现这一目标，我们计划发展免疫和筛查 利用灵长类淋巴细胞群体、人类亚群的策略 功能独特的外周T细胞及其克隆群体 人类T细胞系的群体。一旦这些抗体被识别出来， 我们将把诱导者和抑制者群体分成 表型独特的子集，并调查每个子集的调控 对其他人类T、B细胞和髓系细胞的影响。定义的抗体 以上将被用来描述细胞表面的生物化学特征 他们定义的结构。此外，还将试图澄清 所表征的结构的功能。这些抗体将是有用的 在解剖和描述自身免疫性和非免疫性疾病患者时 免疫调节回路明确的免疫缺陷疾病 不正常。最后，我们将确定T淋巴细胞的少数群体 存在于正常外周血中，并可培养和 确定这些小种群是否有明显和独特的 函数式程序。

The overall aims of the present proposal are directed at the isolation and characterization of unique and still poorly characterized subpopulations of human T lymphocytes with the view that such cells may be centrally involved in the circuits which both up and down regulate the human immune response. The intention is to take advantage of major recent developments in methods for the generation of antibodies to cell surface antigens, for the isolation of purified subpopulations of cells, for the cloning of distinct populations of cells, and lastly for newer methods for the functional analysis of these populations of cells. In the present studies, we plan to undertake a detailed analysis of the phenotypic and functional properties of unique subpopulations of human T lymphocytes. In particular, we plan to develop monoclonal antibody probes to cell surface molecules which can divide the human inducer and suppressor populations into distinct subsets. To accomplish this, we plan to develop immunization and screening strategies which utilize primate lymphocyte populations, subsets of human peripheral T cells and cloned populations of functionally unique populations of human T cell lines. Once these antibodies are identified, we will separate both the inducer and suppressor populations into phenotypically unique subsets and investigate each for their regulatory effects on other human T, B and myeloid cells. The antibodies defined above will be utilized to characterize biochemically the cell surface structures they define. Moreover, attempts will be made to elucidate the function of the structures characterized. These antibodies will be useful in dissecting and characterizing patients with autoimmune and immunodeficiency diseases where the immunoregulatory circuit is clearly abnormal. Lastly, we will identify minor populations of T lymphocytes present both in normal peripheral blood and which can be cultured and determine whether these minor populations have distinct and unique functional programs.