Age-associated changes in the differentiation potentials of human circulating hematopoietic progenitors to T- or NK-lineage cells

• Published in: The Journal of immunology (1950) Vol. 190; no. 12; pp. 6164 - 6172
• Main Authors: Kyoizumi, Seishi, Kubo, Yoshiko, Kajimura, Junko, Yoshida, Kengo, Imai, Kazue, Hayashi, Tomonori, Nakachi, Kei, Young, Lauren F, Moore, Malcolm A, van den Brink, Marcel R M, Kusunoki, Yoichiro
• Format: Journal Article
• Language: English
• Published: United States 15.06.2013
• Subjects: Adult; Aging - immunology; Cell Differentiation - immunology; Cell Lineage - immunology; Cell Separation - methods; Coculture Techniques; Flow Cytometry - methods; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Humans; Immunophenotyping - methods; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1203189

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.