Peripheral and systemic antigens elicit an expandable pool of resident memory CD8⁺ T cells in the bone marrow

BM has been put forward as a major reservoir for memory CD8⁺ T cells. In order to fulfill that function, BM should "store" memory CD8⁺ T cells, which in biological terms would require these "stored" memory cells to be in disequilibrium with the circulatory pool. This issue is a matter of ongoing debate. Here, we unequivocally demonstrate that murine and human BM harbors a population of tissue-resident memory CD8⁺ T (T_RM ) cells. These cells develop against various pathogens, independently of BM infection or local antigen recognition. BM CD8⁺ T_RM cells share a transcriptional program with resident lymphoid cells in other tissues; they are polyfunctional cytokine producers and dependent on IL-15, Blimp-1, and Hobit. CD8⁺ T_RM cells reside in the BM parenchyma, but are in close contact with the circulation. Moreover, this pool of resident T cells is not size-restricted and expands upon peripheral antigenic re-challenge. This works extends the role of the BM in the maintenance of CD8⁺ T cell memory to include the preservation of an expandable reservoir of functional, non-recirculating memory CD8⁺ T cells, which develop in response to a large variety of peripheral antigens.