The impact of aging on memory T cell phenotype and function in the human bone marrow.

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.