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

• Published in: European journal of immunology 2019-06, Vol.49 (6), p.853-872
• Main Authors: Pascutti, Maria Fernanda, Geerman, Sulima, Collins, Nicholas, Brasser, Giso, Nota, Benjamin, Stark, Regina, Behr, Felix, Oja, Anna, Slot, Edith, Panagioti, Eleni, Prier, Julia E., Hickson, Sarah, Wolkers, Monika C., Heemskerk, Mirjam H.M., Hombrink, Pleun, Arens, Ramon, Mackay, Laura K., Gisbergen, Klaas P.J.M., Nolte, Martijn A.
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; CD69; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Frontline ∣ |Basic; Highlights; Hobit; Humans; Immunologic Memory - immunology; Immunological memory; infection; Lymphocytes; Lymphocytes T; Lymphoid cells; Memory cells; Mice; Mice, Inbred C57BL; Parenchyma; resident memory T cells; T-Lymphocyte Subsets - immunology; Transcription
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201848003

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. The memory “reservoir” of the BM contains an expandable population of polyfunctional tissue‐resident memory CD8+ T (TRM) cells, which develop against various pathogens, independently of local infection or antigen recognition. These CD8+ TRM cells reside in the parenchyma, but are in close contact with the circulation.