Tissue resident T cell memory or how the magnificent seven are chilling in the bone

Following infection, tissue-resident memory T cells (Trm) are thought to be left behind at sites of antigen encounter to protect affected tissues against subsequent reinfection. In this issue of the European Journal of Immunology, however, Pascutti et al. demonstrate that both murine and human CD8$^{+}$ Trm specific to seven different pathogens, including systemic, skin, and lung tissue-localized pathogens, accumulate in the bone marrow (BM). These cells have a CD69$^{+}$ phenotype, develop independently of local antigen, and require IL-15, Blimp-1, and Hobit for their differentiation and maintenance. Following restimulation, these cells expand and rapidly produce cytokines. While some of these responses may protect the BM from infection, the consideration that some of these pathogens or their antigens might never reach the BM suggests additional functional roles of BM Trm, possibly in supporting hematopoietic functions via cytokine production following infection. It will be further interesting to determine whether BM Trm contribute to the circulating effector pool following reinfection with tissue-localized or systemic pathogens and whether these cells can be elicited by vaccination