A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127

Nat Immunol. 2006 Nov;7(11):1217-24. doi: 10.1038/ni1395. Epub 2006 Oct 1.

Abstract

Natural killer (NK) cell development is thought to occur in the bone marrow. Here we identify the transcription factor GATA-3 and CD127 (IL-7R alpha) as molecular markers of a pathway of mouse NK cell development that originates in the thymus. Thymus-derived CD127+ NK cells repopulated peripheral lymphoid organs, and their homeostasis was strictly dependent on GATA-3 and interleukin 7. The CD127+ NK cells had a distinct phenotype (CD11b(lo) CD16- CD69(hi) Ly49(lo)) and unusual functional attributes, including reduced cytotoxicity but considerable cytokine production. Those characteristics are reminiscent of human CD56(hi) CD16- NK cells, which we found expressed CD127 and had more GATA-3 expression than human CD56+ CD16+ NK cells. We propose that bone marrow and thymic NK cell pathways generate distinct mouse NK cells with properties similar to those of the two human CD56 NK cell subsets.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • GATA3 Transcription Factor / biosynthesis*
  • GATA3 Transcription Factor / genetics
  • Humans
  • Immunophenotyping
  • Interleukin-7 / physiology
  • Interleukin-7 Receptor alpha Subunit / biosynthesis*
  • Interleukin-7 Receptor alpha Subunit / genetics
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Subsets / cytology*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Signal Transduction / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism

Substances

  • Cytokines
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit