HUMAN T-CELL SUBSETS--ISOLATION AND CHARACTERIZATION

本提案的总体目标是剖析 CD4+记忆或辅助性T细胞群。相当大的进步 近年来已经在功能和表型上取得了进展 存在于CD4+人群中的异质性及其作用 新发现的细胞表面结构在定义 这些细胞的行为。人类亚群的详细分析 CD4+淋巴细胞表明这一群体由AT组成 至少两个，最有可能是几个种群 由各种刺激不同地触发，以获得特定的 函数式程序。在这项拨款提案中，我将集中精力 主要是关于CD4+4B4(CDw29)记忆的特征或 辅助诱导者群体，因为这个群体扮演着核心角色 通过识别召回抗原在免疫反应中的作用， 激活MHC限制性细胞毒T细胞诱导B细胞 免疫球蛋白的合成和分泌多种生物 强效淋巴因子。相当多的证据表明 在艾滋病和艾滋病患者中存在CD4+细胞的全身性缺陷 记忆群体中的缺陷可能是早期的 艾滋病毒感染的表现。很明显， 不仅需要CD4+CDw29+T细胞辅助者的完整性 用于产生特异性抗体，但用于产生MHC 限制的CTL可以抑制HIV病毒的复制 或者杀死感染艾滋病毒的自体靶细胞。我们相信 执行许多这样的功能程序的能力是 部分由这些细胞表面结构决定的 记忆细胞表达和它们产生的细胞因子。这个 这份提案中描述的项目集中在几种抗原上 在包括1F7(CDw26)和 具有二肽基肽酶活性的胞外酶)、180和190 KD LCA(CD45)亚型(蛋白质酪氨酸磷酸‘)和4B4( 纤维连接蛋白受体)和其他结构。我们将描述 表达这些抗原的细胞群体，他们的 细胞因子的释放模式及其分子机制 这些抗原对功能异质性有哪些贡献？ 人类免疫缺陷病毒的数量。拟议的研究应有助于确定 选择功能可能与之相关的CD4细胞群体 淋巴因子的产生和细胞表面的差异 抗原表达。对这一机制的理解 这些细胞影响它们的功能程序应该提供新的 自身免疫性黄斑变性的诊断和治疗 免疫缺陷疾病。

The overall aim of the present proposal is the dissection of the CD4+ memory or helper T cell population. Considerable progress has been made in recent years on the functional and phenotypic heterogeneity that exists within the CD4+ population and the role of newly identified cell surface structures in defining the behavior of these cells. Detailed analysis of subsets of human CD4+ lymphocytes indicate that this population is comprised of at least two and most likely several populations which can be differentially triggered by various stimuli to elicit specific functional programs. In this grant proposal I will concentrate mainly on the characterization of the CD4+4B4(CDw29) memory or helper inducer population since this population plays a central role in the immune response by recognizing recall antigens, activating MHC restricted cytotoxic T cells, inducing B cell immunoglobulin synthesis and secreting a variety of biologically potent lymphokines. Considerable evidence suggests that generalized defects in the CD4+ population exists in AIDS and that defects in the memory population may be one of the early manifestations of HIV infection. It is evident that the integrity of the CD4+CDw29+ T cell helper is required not only for specific antibody production, but for the generation of MHC restricted CTL's which can either inhibit HIV viral replication or kill HIV infected autologous target cells. We believe that the ability to carry out many of these functional programs is dictated in part by the cell surface structures which these memory cells express and the cytokines they produce. The projects described in this proposal focus on several antigens expressed on the CD4+ memory cell including 1F7(CDw26) an ectoenzyme with dipeptidyl-peptidase activity), the 180 and 190 KD LCA (CD45) isoforms (protein tyrosine phosphate') and 4B4 (the fibronectin receptor) and other structures. We will characterize the populations of cells expressing these antigens, their patterns of cytokine release and the molecular mechanisms by which these antigens contribute to the functional heterogeneity of the CD4 population. The proposed studies should help identify populations of CD4 cells whose selective function may be related to both differences in lymphokine production and cell surface antigen expression. An understanding of the mechanism by which these cells effect their functional program should provide new insights into the diagnosis and treatment of autoimmune and immunodeficiency diseases.