HUMAN T CELL SUBSETS: ISOLATION AND CHARACTERIZATION

本提案的总体目标是隔离和 特征的独特和仍然不佳表征亚群的 人T淋巴细胞，认为这些细胞可能是中枢参与的 在调节人体免疫反应的回路中。 其目的是利用方法方面最近的重大发展， 用于产生针对细胞表面抗原的抗体， 分离纯化的细胞亚群，用于克隆不同的 细胞群，最后是功能性的新方法， 分析这些细胞群。 在目前的研究中，我们计划 进行表型和功能特性的详细分析 人类T淋巴细胞的独特亚群。 我们特别计划 开发针对细胞表面分子的单克隆抗体探针， 将人类诱导物和抑制物群体分成不同的亚群。 为了实现这一目标，我们计划开展免疫接种和筛查 利用灵长类淋巴细胞群、人类淋巴细胞亚群 外周血T细胞和功能独特的克隆群体 人T细胞系的群体。 一旦这些抗体被鉴定出来， 我们将把诱导子和抑制子分为 表型独特的子集，并研究每个子集的调节 对其他人T、B和骨髓细胞的影响。 定义的抗体 以上将用于生物化学表征细胞表面 他们定义的结构。 此外，将试图阐明 特征结构的功能。 这些抗体会对 在解剖和描述自身免疫性疾病患者， 免疫调节回路明显 不正常. 最后，我们将识别T淋巴细胞的少数群体， 存在于正常外周血中，并且可以培养， 确定这些少数群体是否有独特的和独特的 功能程序。

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.