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The bone marrow plays a unique role within the immune system. We compared the phenotype and function of virus-specific CD8⁺ T cells from matched samples of human peripheral blood and bone marrow. Analysis of virus-specific memory CD8⁺ T cells showed widely divergent partition of antigen-specific populations between blood and bone marrow. T cells specific for Epstein-Barr virus (EBV) lytic antigens were enriched 3-fold in marrow compared with blood, whereas the response to EBV latent epitopes was equivalent between the 2 compartments. No difference in EBV viral load or expression of the EBV lytic protein was observed between blood and bone marrow. In direct contrast, although cytomegalo-virus (CMV)–specific T cells were the largest virus-specific population within peripheral blood, they were reduced by 60% within marrow. Bone marrow T cells were found to exhibit a unique CCR5 …