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

Overview

MeSH Major

  • Aging
  • Cell Differentiation
  • Hematopoietic Stem Cells
  • Killer Cells, Natural
  • T-Lymphocytes

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.

publication date

  • June 15, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3679208

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1203189

PubMed ID

  • 23670190

Additional Document Info

start page

  • 6164

end page

  • 72

volume

  • 190

number

  • 12