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

Kyoizumi S, Kubo Y, Kajimura J, Yoshida K, Imai K, Hayashi T, Nakachi K, Young LF, Moore MA, van den Brink MRM, Kusunoki Y
J Immunol 2013 (June); 190(12):6164–72
doi: 10.4049/jimmunol.1203189

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.

Reproduced with permission of The Journal of Immunology