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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.

Author information

1
Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
2
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
3
Department of Molecular and Cellular Hemostasis, Sanquin Research, Amsterdam, The Netherlands.
4
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
5
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
6
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

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.

KEYWORDS:

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

PMID:
30891737
DOI:
10.1002/eji.201848003

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