Human bone marrow:: A reservoir for enhanced effector memory CD8+ T cells with potent recall function

The role of human bone marrow (BM) CD8(+) T cells in the immune response to viral Ags is poorly defined. We report here the identification and characterization of a functionally enhanced effector memory CD8(+) T cell population (T-EM) in the BM of patients undergoing total joint replacement for osteoarthritis. These BM-derived T-EM differ strikingly from correlate cells in peripheral blood (PB), expressing elevated levels of CD27, HLA-DR, CD38, CD69, and unique patterns of chemokine receptors. Interestingly, while BM T-EM have low levels of resting perforin and granzyme B, these molecules evidence profound up-regulation in response to TCR stimulation resulting in enhanced cytotoxic potential. Moreover, compared with the T-EM subset in PB, BM CD8(+) T-EM cells demonstrate a more vigorous recall response to pooled viral Ags. Our results reveal that human BM serves as a repository for viral Ag-specific T-EM with great therapeutic potential in vaccine development.