FUNCTIONAL SIGNIFICANCE OF T CELL ACTIVATION MARKERS

描述(改编自《调查者摘要》)：我们已经到了 将特定的表面决定因素的表达与特定的 T细胞分化和活化的各个阶段，并具有一定的功能。 这是一种理性的方法，它假设正在扩张的细胞和 分化效应器功能的获得会表达不同的 基因产物的星座取决于它们在 成熟连续体。通过相关实验和实验 涉及细胞分离，该领域已经开始将诸如 CD45RA和CD62L与免疫幼稚，CD45RO和CD29与记忆，以及 CD25、CD38、人类白细胞抗原-DR等标志物被激活。接受这一点 该方案提出了一个悖论，即在艾滋病和许多其他T细胞反应迟钝 外周循环中优势T细胞群的状态 表达通常与T细胞激活相关的标志物。现在 提案系统地重新评估了 一小群精心挑选的表面决定因素的共同表达。 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(幼稚或未激发，记忆或激发，以及 激活的存储器或效应器)排除一个或多个被 存在于健康中，但在疾病状态中占主导地位，其特征是 淋巴生成压力。这样的群体将在 常见于激活的记忆T细胞，但最终会显示 它们的功能差异(可能是成熟的差异) 不同点。因此，本提案的目标是1) 在多参数中确定主要T细胞群的位置 用四色为新鲜分离的正常外周血T细胞留出空间 流式细胞术，2)测量选择的主要人群的功能 成熟T细胞已知发育阶段和假设发育阶段的区分 细胞；3)对超出正常多参数的总体进行量化 人类免疫缺陷病毒血清阳性受试者和患者干细胞移植后早期的间隙 移植(作为淋巴系统应激的模型)；4)比较 细胞落在正常多参数空间之外的函数，以便 检验新种群代表激活的相互竞争的假说 记忆T细胞或新产生的原性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.