Antigen Responses by CD4 T cells of the Aged

描述：(逐字摘自申请表)我们的目标是推动我们的 对慢性阻塞性肺疾病中抗原特异性CD4T细胞反应下降的认识 年纪大了。在目标1中，我们将确定是否所有初始的CD4细胞都有IL-2缺陷 如果缺陷被归类为T细胞亚群，如 罗丹明123细胞。我们将使用T细胞受体(TCR)转基因TG小鼠 与IL-2基因被cdna替换的突变小鼠品系杂交 编码绿色荧光蛋白以进行与年龄相关的比较 IL-2产生细胞的频率和产生IL-2的相对数量 手机。老龄化环境对幼稚T细胞功能的影响将是 采用收养转移方式确定的。我们将确定IL-2缺乏是否 可通过与炎性细胞因子或 用更高亲和力的多肽进行刺激。在目标2中，我们将定义与年龄相关的 CD4记忆反应的改变。我们将对过继转移的人进行免疫 幼龄/老年小鼠幼稚TG+CD4T细胞及恢复记忆分析 细胞的表型、频率及其分化为效应器的能力 在体外用抗原重新刺激细胞。记忆效应细胞功能 也将接受评估。我们将确定老年人的贡献 环境对转移幼年TG+CD_4细胞产生记忆反应的影响 T细胞移植给年轻/老年宿主。如果反应随着年龄的增长而减弱，我们将 确定添加IL-2或炎性细胞因子是否会恢复 响应性。在目标3中，我们将确定人的寿命是否发生变化 老年人外周血中CD4T细胞在IL-2缺乏中的作用 制作。通过采用细胞移植，我们将确定T细胞的差异 细胞寿命、周转和生存/凋亡因子的表达。我们会 根据主持人的年龄确定贡献 长寿/营业额/存活率。我们会操纵条件，这样我们就可以 诱导年轻细胞“老化”(即延长寿命)，反之亦然 确定这些操作是否会导致抗原特异性改变 功能(即产生IL-2)。

DESCRIPTION: (Verbatim from application) Our goal is to further our understanding of the decline in antigen-specific CD4 T cell responses in the aged. In Aim 1, we will determine if all naive CD4 cells are defective in IL-2 production or if the defect is relegated to T cell subsets such as the Rhodamine 123dim cells. We will use T cell receptor (TcR) transgenic Tg) mice crossed with a mutant mouse strain in which the IL-2 gene is replaced with cDNA encoding green fluorescent protein to make age-related comparisons in the frequency of IL-2 producing cells and the relative amount of IL-2 produced per cell. The impact by the aged environment on naive T cell function will be determined using adoptive transfer. We will determine if the IL-2 deficiency can be overcome through co-immunization with inflammatory cytokines or stimulation with higher affinity peptides. In Aim 2, we will define age-related alterations in the CD4 memory response. We will immunize adoptively transferred naive Tg+ CD4 T cells from young/old mice and analyze the recovered memory cells for phenotype, frequency and their ability to differentiate into effector cells upon restimulation with antigen in vitro. Memory effector cell function will also be evaluated. We will determine the contribution by the aged environment on the generation of memory responses by transferring young Tg+ CD4 T cells to young/aged hosts. if responses are diminished with aging, we will determine if the addition of IL-2 or inflammatory cytokines restores responsiveness. In Aim 3 we will determine if alterations in the longevity of CD4 T cells in the periphery of the aged contribute to the deficiency in IL-2 production. Using adoptive cell transfer we will determine differences in T cell longevity, turnover and expression of survival/apoptotic factors. We will determine the contribution by the age of the host on longevity/turnover/survival. We will manipulate conditions such that we may induce young cells to "age" (i.e., increased longevity) and vice versa, and determine if these manipulations induce alterations in antigen specific function (i.e., IL-2 production).