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 naive 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. J. Leukoc. Biol. 91: 197-205; 2012.