Antigen Responses by CD4 T cells of the Aged

描述：（逐字从应用程序）我们的目标是进一步我们的 了解在抗原特异性CD 4 T细胞反应的下降， 老了在目标1中，我们将确定是否所有初始CD 4细胞都是IL-2缺陷的， 生产或如果缺陷是降级到T细胞亚群，如 罗丹明123dim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，以进行年龄相关的比较， 产生IL-2的细胞的频率和每个细胞产生IL-2的相对量 cell.老年环境对幼稚T细胞功能的影响将是 通过过继转移确定。我们将确定白细胞介素2缺乏症 可以通过与炎性细胞因子共免疫来克服， 用更高亲和力的肽刺激。在目标2中，我们将定义与年龄相关的 CD 4记忆反应的改变。我们将免疫收养转移 来自年轻/年老小鼠的初始Tg+ CD 4 T细胞，并分析恢复的记忆 细胞的表型、频率及其分化为效应细胞的能力 在体外用抗原再刺激细胞。记忆效应细胞功能 也将进行评估。我们将确定老年人的贡献 环境对通过转移年轻的Tg+ CD 4产生记忆反应的影响 T细胞对年轻/老年宿主的免疫应答。如果反应随着年龄的增长而减弱， 确定IL-2或炎性细胞因子的加入是否能恢复 响应能力。在目标3中，我们将确定， 老年人外周血CD 4 T细胞参与IL-2的缺乏 生产使用过继细胞转移，我们将确定T 细胞寿命、更新和存活/凋亡因子的表达。我们将 根据主机的年龄确定贡献， 寿命/周转率/生存率。我们会操纵条件， 诱导年轻细胞“老化”（即，增加寿命），反之亦然， 确定这些操作是否诱导抗原特异性 函数（即，IL-2产生）。

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).