Commitment of common T/Natural killer (NK) progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay

J Exp Med. 1999 Dec 6;190(11):1617-26. doi: 10.1084/jem.190.11.1617.

Abstract

We have established a new clonal assay system that can evenly support the development of T and natural killer (NK) cells. With this system, we show that all T cell progenitors in the earliest CD44(+)CD25(-)FcgammaRII/III(-) fetal thymus (FT) cell population retain NK potential, and that the NK lineage-committed progenitors (p-NK) also exist in this population. T cell lineage-committed progenitors (p-T), which are unable to generate NK cells, first appear at the CD44(+)CD25(-) FcgammaRII/III(+) stage in day 12 FT. The proportion of p-T markedly increases during the transition from the CD44(+)CD25(-) stage to the CD44(+)CD25(+) stage in day 14 FT. On the other hand, p-NK preferentially increase in number at the CD44(+)CD25(-) stage between days 12 and 14 of gestation. The production of p-NK continues up to the CD44(+)CD25(+) stage, but ceases before the rearrangement of T cell receptor beta chain genes. It was further shown that the CD44(+)CD25(-) CD122(+) population of day 14 FT exclusively contains p-NK. These results indicate that the earliest T cell progenitor migrating into the FT is T/NK bipotent, and strongly suggest that the bipotent progenitor continuously produces p-NK and p-T until the CD44(+)CD25(+) stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cytokines / pharmacology*
  • Fetus
  • Flow Cytometry
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology*
  • Immunophenotyping
  • Interleukins / pharmacology*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Organ Culture Techniques
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / immunology*
  • Thymus Gland / embryology*
  • Thymus Gland / immunology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Cytokines
  • Interleukins
  • Recombinant Proteins