title: 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 CD127(hi) effluxers are conventional CD8(+) T cells exhibiting a broad TCR-Vβ repertoire and are generated in response to viral peptides in vitro. CD127(hi) effluxer CD8(+) T cells have an early memory phenotype defined by preferential TNF-α production and a Bcl-2(hi) , KLRG-1(low) 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 CD127(hi) effluxer CD8(+) T cells in vitro. Consequently, the CD127(low) effluxer subset may comprise cells recently exposed to IL-15. Taken together, CD127(hi) effluxer CD8(+) T cells represent a novel population of early memory T cells resident in BM with properties required for long-lived memory.
authors.affiliation: Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kudernatsch
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.forename: Manuel
authors.initials: M
authors.lastname: Guerreiro
authors.forename: Madlen
authors.initials: M
authors.lastname: Löbel
authors.forename: Sandra
authors.initials: S
authors.lastname: Bauer
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
mesh_terms: D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D019409:Interleukin-15 / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology*; D019394:Ki-67 Antigen / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011971:Receptors, Immunologic; D015534:Trans-Activators / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C569274:IL15 protein, human; D019409:Interleukin-15; D053699:Interleukin-7 Receptor alpha Subunit; C113413:KLRG1 protein, human; D019394:Ki-67 Antigen; D037181:Lectins, C-Type; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha
keywords: Bone marrow; CD127; Early memory; Efflux; Memory CD8+ T cells