PHENOTYPE OF ANTIGEN SPECIFIC T CELLS DURING AGING

随着年龄的增长，功能和功能都发生了实质性的变化 人类和啮齿动物T细胞的表型图谱。在这些人中 老年人发生的功能变化是轮廓的改变 细胞因子的产生，信号转导早期事件的变化 对TCR和共刺激因子的反应降低了细胞的增殖- 中介刺激。在表型变化中，有一个戏剧性的转变 朝向增加的存储单元的比例并伴随着下降 幼稚细胞的比例。尽管许多与年龄相关的人 功能的改变被认为是这一人群的结果 转移，叠加在这上面的很可能是内在的变化 功能。使用TCR转基因小鼠模型，我们将解决以下问题 问题：1)老年人是否由于抗原性而转变为记忆表型 刺激？；2)哪些变化与“老年表型”有关 可归因于老化过程与向存储单元的转变 优势？；3)由于暴露于环境抗原 在人的一生中，反复接触抗原会有什么影响 有无响应性？；4)那些切换到记忆表型的细胞， 它们能像对年轻人的抗原一样对抗原产生反应吗？(即，是 抗原特异性记忆细胞能够做出反应的比例 随着年龄的增长而减少？是抗原反应细胞的频率 减少了？在每个细胞的基础上，是响应的平均水平 降低？)；5)记忆T细胞反应性的哪些过程 年龄发生改变(即CTL和CTL的代数是否下降 CD4效应器？CTL或CD4反应性是否下降？)；6)可以 我们阐明了年龄相关改变的任何机制(S) (即，细胞因子的产生和年龄是否有任何与年龄相关的变化 受体表达、Fas和P-糖蛋白表达等)？；7) 同样的问题可能也适用于少数幼稚细胞 是在老年人身上发现的。这些简单但重要的答案 这些问题将影响为老年人接种疫苗的策略。

With aging, substantial changes occur in both the functional and phenotypic profiles of T cells in humans and rodents. Among the functional changes that occur in the aged are alterations in the profile of cytokines produced, changes in the early events of signal transduction and decreased cellular proliferation in response to TCR- and costimulus- mediated stimulation. Among the phenotypic changes is a dramatic shift toward an increased proportion of memory cells with a concomitant decline in the proportion of naive cells. Although many of the age-associated functional changes are proposed to be the consequence of this population shift, superimposed on this are likely to be intrinsic changes in function. Using TCR transgenic mouse models we will address the following issues: 1) Is the shift to a memory phenotype in the aged due to antigenic stimulation?; 2) Which alterations associated with the "aged phenotype" are attributable to the aging process vs. the shift to memory cell predominance?; 3) Since exposure to environmental antigens occurs throughout one's lifetime, what effect does repeated exposures to antigen have on responsiveness?; 4) Of those cells switched to a memory phenotype, can they respond to antigen as well as those from the young? (i.e., Is the proportion of antigen-specific memory cells capable of responding decreased with age? Is the frequency of antigen-responsive cells decreased? On a per cell basis, is the average level of responsiveness decreased?); 5) Which processes of memory T cell responsiveness in the aged are altered (i.e., Is there a decline in the generation of CTL and CD4 effectors? Is there a decline in CTL or CD4 responsiveness?); 6) Can we elucidate any mechanism(s) involved in the age-associated alterations (i.e., Are there any age-associated alterations in cytokine production and receptor expression, fas and P-glycoprotein expression, etc.)?; 7) The same questions may be addressed to the small population of naive cells that are found in the aged. Answers to these simple yet important questions will affect strategies for vaccinating the elderly.