PHENOTYPE OF ANTIGEN SPECIFIC T CELLS DURING AGING

随着年龄的增长，在功能和 人类和啮齿类动物中T细胞的表型谱。 中 发生在老年人中的功能变化是轮廓的改变， 细胞因子的产生，信号转导的早期事件的变化 并降低细胞增殖对TCR和共刺激的反应， 介导的刺激。 在表型变化中， 随着记忆细胞比例的增加， 幼稚细胞的比例。 尽管许多与年龄相关的 功能变化被认为是该种群的结果 转变，叠加在这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）老年人记忆表型的转变是否由于抗原性 刺激？2)哪些改变与“衰老表型”相关 是由于老化过程与转移到存储单元 优势？3)由于暴露于环境抗原 在人的一生中，反复接触抗原 是否有响应能力？4)在那些转变为记忆表型的细胞中， 它们对抗原的反应是否和年轻时一样？(i.e.,是 抗原特异性记忆细胞的比例 随着年龄的增长而减少？ 是抗原反应细胞的频率 减少？ 在每个细胞的基础上，是反应的平均水平 下降？）; 5)记忆T细胞反应性的过程 年龄被改变（即，CTL的产生是否有所下降， CD 4效应细胞？ CTL或CD 4反应性是否下降？）; 6)可以 我们阐明了与年龄相关的变化所涉及的任何机制， (i.e.,是否有任何与年龄相关的细胞因子产生的变化， 受体表达、Fas和P-糖蛋白表达等）; 7)的 同样的问题也可以针对小群体的幼稚细胞 在老年人身上发现的。 这些简单而重要的问题的答案 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.