The bone marrow environment maintains polyfunctional memory T cells during human aging (132.12)

Abstract The bone marrow (BM) has recently been attributed a key role in memory T cell maintenance. However, little is still known about the distribution, phenotype and function of human T cell subsets in the BM and how aging affects BM T cell function and survival. Here we show that human BM T cells are in a heightened activation state and express a characteristic set of chemokine- and co-stimulatory receptors compared to peripheral blood (PB). BM T cells also rapidly proliferate upon stimulation with anti-CD3 and IL-15. Moreover, the number of polyfunctional CD4 and CD8 T cells was higher in the BM compared to the PB. Aging led to a decline of naive T cells and to an accumulation of cells with an effector/effector-memory phenotype in the BM. Though, the age-related increase in highly differentiated CD57-expressing effector CD8 T cells was much lower in the BM compared to the PB. During aging, the frequency of polyfunctional BM T cells was maintained. The expression of IL-6 was increased during aging in the BM and together with IL-15 might contribute to the sustained activation of memory T cells in the BM. Gene array analysis also revealed a potential cytokine network responsible for the age-related increase in IL-6 expression. In conclusion, our results indicate that the BM environment is important for the maintenance of polyfunctional memory CD4 and CD8 T cells during human aging.