Maintenance of memory CD8 T cells: Divided over division

Once generated during an infection, memory CD8⁺ T cells can provide long-lasting protection against reinfection with an intracellular pathogen, but the longevity of this defense depends on the ability of these pathogen-specific memory cells to be maintained. It is generally believed that the bone marrow plays an important role in this respect, where memory CD8 T cells receive reinvigorating signals from cytokines that induce homeostatic proliferation. However, in the current issue of the European Journal of Immunology, Siracusa et al. (Eur. J. Immunol. 2017. 47: 1900-1905) argue against this dogma, as they provide evidence that CD8 memory T cells in murine bone marrow are not proliferating, but largely quiescent, which protects them from elimination by the cytostatic drug Cyclophosphamide. Interestingly, this is in sharp contrast to the proliferating cell counterparts in the spleen, which are eliminated by this treatment. Here, we will discuss the impact of these results, how they relate to opposing findings by others in the field, and what the relevance of these findings is for humans and clinical applications.