FUNCTIONAL SIGNIFICANCE OF T CELL ACTIVATION MARKERS

描述（改编自研究者摘要）：我们已经来到 将特定表面决定因素的表达与特定 T细胞的分化和活化阶段，并具有一定的功能。 这是一种合理的方法，它假设细胞经历扩增， 获得分化效应子功能将表达不同的 基因产物的星座取决于它们在一个 成熟连续体 通过相关实验和试验 在涉及细胞分离的情况下，该领域已经开始将标记物如 CD 45 RA和CD 62 L具有免疫幼稚性，CD 45 RO和CD 29具有记忆性， 标志物如CD 25、CD 38和HLA-DR具有活化。 接受本 该方案提出了一个悖论，即在艾滋病和许多其他T细胞低反应， 调节外周循环中的主要T细胞群 表达通常与T细胞活化相关的标志物。 本 建议系统地重新评估的功能意义， 一小组精心挑选的表面决定簇的共表达。 指导这一分析的是一个基本概念，即目前公认的 成熟T细胞的类别（幼稚或未致敏的，记忆或致敏的，以及 激活的记忆或效应器）排除一个或多个群体， 存在于健康状态，但主要表现为以下特征的疾病状态 淋巴细胞生成应激 这样的群体将具有表型属性， 与激活的记忆T细胞一样，但最终会显示 由于其功能（也许是成熟） 相异之处 因此，本提案的目标是： 确定多参数中主要T细胞群的位置 使用4-色法分离新鲜分离的正常外周血T细胞的空间 流式细胞术，2）测量选择的主要群体的功能， 区分成熟T细胞的已知和假定发育阶段 细胞; 3）量化超出正常多参数范围的群体 干细胞移植后早期HIV血清阳性受试者和患者的空间 移植（作为淋巴细胞生成应激的模型）; 4）比较 落在正常多参数空间之外的细胞的功能， 测试竞争的假设，即新的人口代表激活 记忆T细胞或新产生的原活化T细胞。

DESCRIPTION (Adapted from the Investigator's Abstract): We have come to associate the expression of particular surface determinants with particular stages of T cell differentiation and activation and with certain functions. This is a rational approach that assumes that cells undergoing expansion and acquisition of differentiation effector functions will express different constellations of gene products depending on their position in a maturational continuum. Through correlative experiments and experiments involving cell separation, the field has come to associate markers such as CD45RA and CD62L with immunological naivet, CD45RO and CD29 with memory, and markers such as CD25, CD38 and HLA-DR with activation. Acceptance of this scheme raises the paradox that in AIDS and many other T-cell hyporesponsive conditions the predominant T-cell population in the peripheral circulation expresses markers commonly associated with T-cell activation. The present proposal systematically re-evaluates the functional significance of co-expression of a small group of carefully chosen surface determinants. Guiding this analysis is the underlying notion that the presently accepted categories of mature T cells (naive or unprimed, memory or primed, and activated memory or effector) exclude a population or populations which are present in health but predominate in disease states characterized by lymphopoietic stress. Such a population would have phenotypic attributes in common with activated memory T cells, but would ultimately display differences resulting from their functional (and perhaps maturational) dissimilarities. The objectives of the present proposal, therefore, are 1) to determine the location of major T cell populations in multi-parameter space for freshly isolated normal peripheral blood T cells using 4-color flow cytometry, 2) to measure functions of the major populations chosen to discriminate between known and postulated developmental stages of mature T cells; 3) to quantify populations falling outside of normal multi-parameter space in HIV seropositive subjects and patients early after stem cell transplantation (as a model for lymphopoietic stress); 4) to compare the function of cells falling outside of normal multiparameter space in order to test the competing hypotheses that novel populations represent activated memory T-cells or newly generated pronaive T-cells.