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

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 (TRM ) cells. These cells develop against various pathogens, independently of BM infection or local antigen recognition. BM CD8+ TRM cells share a transcriptional program with resident lymphoid cells in other tissues; they are poly-functional cytokine producers and dependent on IL-15, Blimp-1 and Hobit. CD8+ TRM 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. This article is protected by copyright. All rights reserved. Overall design: In total 3 sorts were done, and for each sort the 8 T cell populations were isolated from a pool of 6 mice. The quality of the RNA sample of RM T cells of sort 4 was poor and therefore removed from analysis.