title: Age-associated changes in the differentiation potentials of human circulating hematopoietic progenitors to T- or NK-lineage cells.
abstract: Age-associated changes of T and NK cell (T/NK) potential of human hematopoietic stem cells are unknown. In this study, we enumerate and characterize T/NK precursors among CD34(+)Lin(-) cell populations circulating in normal human adult peripheral blood (PB) by a limiting-dilution assay using coculture with OP9-DL1 stroma cells expressing Notch 1 ligand, Delta-like 1. The frequency of T cell precursors in CD34(+)Lin(-) cells was found to decrease with donor age, whereas the ratio of NK to T cell precursor frequency (NK/T ratio) increased with age, suggesting that lymphoid differentiation potential of PB progenitors shifts from T to NK cell lineage with aging. Clonal analyses of CD34(+)Lin(-) cells showed that differences in the NK/T ratio were attributable to different distributions of single- and dual-lineage T/NK precursor clones. Because nearly all of the clones retained monocyte and/or granulocyte differentiation potentials in coculture with OP9-DL1 cells, T/NK precursors in PB are considered to be contained in the pool of T/NK/myeloid multipotent progenitors. The age-associated increase in NK over T cell commitment might occur in precursor cells with T/NK/myeloid potential.
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan. kyoizumi@rerf.or.jp
authors.forename: Seishi
authors.initials: S
authors.lastname: Kyoizumi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kubo
authors.forename: Junko
authors.initials: J
authors.lastname: Kajimura
authors.forename: Kengo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kazue
authors.initials: K
authors.lastname: Imai
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Lauren F
authors.initials: LF
authors.lastname: Young
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Moore
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusunoki
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D018920:Coculture Techniques; D005434:Flow Cytometry / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology