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Eur J Immunol. 2019 Mar 20. doi: 10.1002/eji.201848003. [Epub ahead of print]

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

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Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Department of Molecular and Cellular Hemostasis, Sanquin Research, Amsterdam, The Netherlands.
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.


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 polyfunctional 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.


CD69; Hobit; bone marrow; infection; resident memory T cells


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