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

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.

CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17

“…Improved responses to anti-PD-1 in patients with high densities of tumor CD103 + CD8 + T RM cells, even after having undergone resection of their tumor, may be associated with a pool of cancer-specific CD8 + T cells present in bone marrow, as has been described in infectious diseases. 54 This non-circulating memory CD8 + T cell subset develops in response to a wide variety of antigens, including tumor antigens, and expands upon antigen rechallenge. Thus, CD103 + CD8 + T RM cells appear to be crucial components in immune protection against cancer and in the response of NSCLC to ICB, opening up new avenues in cancer immunotherapy.…”

Organ-Specific Surveillance and Long-Term Residency Strategies Adapted by Tissue-Resident Memory CD8+ T Cells

“…In addition to the well-studied epidermis and small intestinal epithelium that are constitutively exposed to microbes, T RM lodge to organs that are less subjected to constant microbial challenge and contain few or no E-cadherin-expressing epithelial layers. These organs include CNS, kidney, submandibular salivary glands (SMG), liver, and bone marrow ( 10 , 16 , 75 , 76 ). In contrast to epidermis where CD8 + T RM are embedded between non-vascularized epithelial cells, these complex organs contain extensive blood and lymphatic vascular systems, innervation, fibroblasts, tissue-resident macrophages, and innate immune cells, as well as in some cases arborized secretory epithelium.…”

New Insights into Mechanisms of Long-term Protective Anti-tumor Immunity Induced by Cancer Vaccines Modified by Virus Infection

“…These cells, being dependent on IL-15, reside in BM parenchyma ("chilling in the bone" [76]). They represent a pool of resident MTCs in close contact with the blood circulation and expandable upon peripheral or systemic antigen re-challenge [77].…”