Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria.
J Leukoc Biol. 2012 Feb;91(2):197-205. doi: 10.1189/jlb.0611299. Epub 2011 Oct 19.
Recently, the BM has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4⁺ and CD8⁺ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of naïve and an increase in T(EM) cells. In contrast to the PB, a highly activated CD8⁺CD28⁻ T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation, and differentiation of CD8⁺ T cells in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8⁺CD28⁻ T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4⁺ and CD8⁺ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8⁺CD28⁻ T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age.
最近，BM 被证明在调节记忆 T 细胞的存活和功能方面发挥着关键作用。然而，衰老对这些过程的影响尚未得到研究。我们证明，在衰老过程中，BM 中的 CD4⁺和 CD8⁺T 细胞数量得以维持。然而，衰老 BM 中 T 细胞库的组成发生了改变，幼稚细胞减少，T(EM)细胞增加。与 PB 不同，在老年人的 BM 中积累了高度活化的 CD8⁺CD28⁻T 细胞群体，该群体缺乏晚期分化标志物 CD57。在衰老的 BM 中增加的 IL-6 和 IL-15 可有效地在体外诱导 CD8⁺T 细胞的激活、增殖和分化，这突出了这些细胞因子在 BM 中高度活化的 CD8⁺CD28⁻T 细胞的年龄依赖性积累中的作用。然而，这些与年龄相关的变化并没有损害老年人 BM 中大量多功能记忆 CD4⁺和 CD8⁺T 细胞的维持。总之，衰老导致 BM 中积累了高度活化的 CD8⁺CD28⁻T 细胞群体，这是由 IL-6 和 IL-15 的年龄相关性增加所驱动的。尽管发生了这些变化，衰老的 BM 仍然是多功能记忆 T 细胞的丰富来源，因此可能代表着老年时抵抗复发性感染的重要防线。
