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。 相当大的进展 近年来，在功能和表型方面， 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， 这些细胞的行为。 详细分析了人类 CD4+淋巴细胞表明，这一群体是由在 至少有两个，最有可能是几个群体， 由不同的刺激不同地触发， 功能程序。 在这份拨款申请中， 主要是对CD4+4B4（CDw29）记忆的表征，或 辅助诱导物群体，因为该群体起着中心作用， 通过识别回忆抗原在免疫应答中的作用， 激活MHC限制性细胞毒性T细胞，诱导B细胞 免疫球蛋白合成和分泌多种生物活性 强效淋巴因子 大量证据表明， 在艾滋病患者中存在CD4+细胞的普遍缺陷， 记忆人口中的缺陷可能是早期 艾滋病毒感染的表现。 很明显 CD4+CDw29+辅助性T细胞的完整性不仅是必需的， 产生特异性抗体，但产生MHC 可以抑制HIV病毒复制的限制性CTL 或杀死HIV感染的自体靶细胞。 我们认为 执行许多这些功能程序能力 这部分取决于细胞表面结构， 记忆细胞表达和它们产生的细胞因子。 的 本提案中描述的项目集中于几种抗原 表达于包括1F7（CDw26）的CD4+记忆细胞上， 具有二肽基肽酶活性的胞外酶），180和190 KD LCA（CD45）同种型（蛋白酪氨酸磷酸盐）和4B4（ 纤连蛋白受体）和其它结构。 我们将描述 表达这些抗原的细胞群，其 细胞因子释放的模式和分子机制， 这些抗原导致了 CD4人群。 拟议的研究应有助于确定 CD4细胞群，其选择功能可能与 淋巴因子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， 对自身免疫性疾病的诊断和治疗的见解， 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.