Longevity and turnover of human naive T cells in lymphoid tissue

描述(申请人提供)：人体胸腺是T淋巴细胞产生、成熟和输出到外周的必需器官，在外周协调适应性免疫反应。幼稚的T细胞是通过儿童早期的胸腺生成产生的，随后胸腺功能逐渐减少，青春期开始的功能器官体积随着年龄的增长而退化。目前尚不清楚人类原始T细胞是如何以及是否在整个生命过程中胸腺输出减少的情况下保持的，主要是因为对人类T细胞发育的研究一直局限于外周血样本。幼稚T细胞存活的问题和胸腺输出在T细胞再繁殖中的作用，对于理解老年人有效免疫反应的保存具有特别重要的意义。随着年龄的增长，原始T细胞池的大小既受到胸腺输出减少的影响，也受到暴露于抗原后转变为效应记忆细胞的影响。在这里，我们提出了一种新的方法，通过研究从单个器官捐赠者分离的初级和次级淋巴组织中的T细胞群，来研究人类T细胞发育和动态平衡的动态。这项拟议的研究结果将不仅对与衰老有关的免疫学领域产生影响，而且将提供关于幼稚T细胞如何在以前未表现出特征的组织中分布和维持的新信息。此外，拟议的研究将有助于促进对新病原体或疫苗的免疫反应，同时加深对随着年龄增长可能发生的免疫失调机制的理解。

DESCRIPTION (provided by applicant): The human thymus is required for the generation, maturation, and export of T lymphocytes to the periphery where they coordinate adaptive immune responses. Naive T cells are generated via thymopoiesis in early childhood followed by a gradual reduction in thymic function and an age-dependent involution of the functional organ volume beginning in puberty. It is not understood how and whether human naive T cells are maintained in the context of decreasing thymic output throughout life, mainly because studies on human T cell development have been limited to the sampling of peripheral blood. The issue of naive T cell survival and the role of thymic output in repopulation of T cells is of particular relevance in understanding the preservation of an effective immune response in aging individuals. With increasing age, size of the naive T cell pool is affected both by a decrease in thymic export and a transition into effector memory cells following exposure to antigen. We propose here a new approach to study the dynamics of human T cell development and homeostasis by investigating T cell populations in primary and secondary lymphoid tissue isolated from individual organ donors. Results from the proposed study will have implications not only in the field of immunology which pertains to aging but will provide new information of how naive T cells are distributed and maintained in tissues not previously characterized. Furthermore the proposed research will be of relevance to promoting immune responses to new pathogens or vaccines while furthering the understanding of mechanisms for immune dysregulations that can occur with advancing age.