title: Human bone marrow hosts polyfunctional memory CD4+ and CD8+ T cells with close contact to IL-15-producing cells.
abstract: Recently, a key role in memory T cell homing and survival has been attributed to the bone marrow (BM) in mice. In the human BM, the repertoire, function, and survival niches of CD4(+) and CD8(+) T cells have not yet been elucidated. In this study, we demonstrate that CD4(+) and CD8(+) effector memory T cells accumulate in the human BM and are in a heightened activation state as revealed by CD69 expression. BM-resident memory T cells produce more IFN-γ and are frequently polyfunctional. Immunofluorescence analysis revealed that CD4(+) and CD8(+) T cells are in the immediate vicinity of IL-15-producing BM cells, suggesting a close interaction between these two cell types and a regulatory role of IL-15 on T cells. Accordingly, IL-15 induced an identical pattern of CD69 expression in peripheral blood CD4(+) and CD8(+) T cell subsets. Moreover, the IL-15-inducible molecules Bcl-x(L), MIP-1α, MIP-1β, and CCR5 were upregulated in the human BM. In summary, our results indicate that the human BM microenvironment, in particular IL-15-producing cells, is important for the maintenance of a polyfunctional memory CD4(+) and CD8(+) T cell pool.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, 6020 Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Herndler-Brandstetter
authors.forename: Katja
authors.initials: K
authors.lastname: Landgraf
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jenewein
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.forename: Regina
authors.initials: R
authors.lastname: Brunauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.forename: Walther
authors.initials: W
authors.lastname: Parson
authors.forename: Frank
authors.initials: F
authors.lastname: Kloss
authors.forename: Robert
authors.initials: R
authors.lastname: Gassner
authors.forename: Günter
authors.initials: G
authors.lastname: Lepperdinger
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology*; D037181:Lectins, C-Type / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019409:Interleukin-15; D037181:Lectins, C-Type; D000099192:CD69 Antigens