Cunningham C P, Kimpton W G, Holder J E, Cahill R N
Laboratory for Foetal and Neonatal Immunology, The University of Melbourne, Parkville, Australia.
Eur J Immunol. 2001 Mar;31(3):802-11. doi: 10.1002/1521-4141(200103)31:3<802::aid-immu802>3.0.co;2-p.
A diverse repertoire among peripheral T cells is established in early life by thymic export when the naive T cell pool is first formed. In contrast, during adult life the thymus has been thought to play only a minor role in T cell homeostasis. As individuals age there is an increasing proportion of peripheral T cells bearing a memory phenotype, as well as a corresponding decrease in the number of naive T cells. The change in the composition of the peripheral T cell pool with age is thought to occur as a result of reduced or completely curtailed thymic export following thymic involution at puberty together with the antigen-driven expansion of naive T cells in the periphery. We examined thymic export throughout life in fetal, neonatal and aged sheep. We found that the thymus in adult animals showed an efficiency of production and export on a per gram basis equivalent to that observed for much younger animals, and continued to export substantial numbers of T cells long after puberty. The data demonstrate that naive T cells constantly enter the peripheral T cell pool at the same rate throughout fetal, neonatal and adult life, and that one in every 50 T cells in the peripheral lymphoid tissues of aged sheep had emigrated from the thymus in the previous 24 h. The data suggest that restoration by the thymus of a normal peripheral T cell repertoire in chronic T cell-depleting conditions should be possible in adult patients, provided the thymus is not damaged by disease or therapy.
在生命早期，当初始T细胞库首次形成时，胸腺输出建立了外周T细胞的多样化库。相比之下，在成年期，胸腺被认为在T细胞稳态中仅起次要作用。随着个体年龄增长，具有记忆表型的外周T细胞比例增加，同时初始T细胞数量相应减少。外周T细胞库组成随年龄的变化被认为是青春期胸腺退化后胸腺输出减少或完全停止，以及外周初始T细胞抗原驱动扩增的结果。我们研究了胎儿、新生儿和老年绵羊一生中的胸腺输出。我们发现成年动物的胸腺每克产生和输出的效率与年轻得多的动物相当，并且在青春期后很长时间仍继续输出大量T细胞。数据表明，在胎儿期、新生儿期和成年期，初始T细胞始终以相同的速率不断进入外周T细胞库，并且在老年绵羊外周淋巴组织中，每50个T细胞中就有1个在前24小时内从胸腺迁出。数据表明，在慢性T细胞耗竭的情况下，只要胸腺未因疾病或治疗而受损，成年患者的胸腺就有可能恢复正常的外周T细胞库。
