Human bone marrow contains a subset of quiescent early memory CD8+ T cells characterized by high CD127 expression and efflux capacity

Abstract

Even today it is still not completely understood how CD8+ T-cell memory is maintained long term. Since bone marrow (BM) is a niche for immunological memory, we sought to identify long-lasting early memory CD8+ T cells in this compartment. To achieve this, we looked for CD8+ T cells that are able to efflux Rhodamine 123, a typical property of stem cells. Indeed, we identified a distinct subset of CD8+ T cells in BM, with the capacity to efflux and high CD127 expression. These CD127hi effluxers are conventional CD8+ T cells exhibiting a broad TCR-Vβ repertoire and are generated in response to viral peptides in vitro. CD127hi effluxer CD8+ T cells have an early memory phenotype defined by preferential TNF-α production and a Bcl-2hi, KLRG-1low profile. This population has long telomeres and shows constitutively low frequencies of Ki-67 expression ex vivo, but has a high proliferative and differentiation capacity in vitro. However, IL-15 downmodulates CD127 in CD127hi effluxer CD8+ T cells in vitro. Consequently, the CD127low effluxer subset may comprise cells recently exposed to IL-15. Taken together, CD127hi effluxer CD8+ T cells represent a novel population of early memory T cells resident in BM with properties required for long-lived memory.