Differential roles for IL-15R alpha-chain in NK cell development and Ly-49 induction

J Immunol. 2003 Nov 15;171(10):5085-90. doi: 10.4049/jimmunol.171.10.5085.

Abstract

IL-15Ralpha-deficient (IL-15Ralpha(-/-)) mice lack NK cells. However, when bone marrow (BM) progenitors from IL-15Ralpha(-/-) mice were cultured with IL-7, stem cell factor and flt3 ligand, followed by IL-15, they were able to differentiate into functional NK cells, indicating that IL-15Ralpha is not critical for NK cell development. Whereas NK cells generated in vitro from IL-15Ralpha(-/-) BM progenitors expressed CD94/NKG2, they failed to express Ly-49 receptors. In keeping with this, when IL-15Ralpha(-/-) BM cells were transferred into wild type recipients, they gave rise to NK cells in vivo, but with greatly reduced expression of Ly-49 receptors. Furthermore, the small numbers of NK cells found in IL-15(-/-) as well as IL-15Ralpha(-/-) but not flt3 ligand(-/-) mice expressed much lower levels of Ly-49 receptors than those from wild type mice. These results indicate a novel role for IL-15Ralpha-chain in Ly-49 induction on developing NK cells.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Ly / biosynthesis*
  • Antigens, Ly / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Interleukin-15 / deficiency
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lectins, C-Type
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Subunits / biosynthesis
  • Protein Subunits / deficiency
  • Protein Subunits / genetics
  • Protein Subunits / physiology*
  • Radiation Chimera / genetics
  • Radiation Chimera / immunology
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / biosynthesis
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / physiology*
  • Receptors, NK Cell Lectin-Like

Substances

  • Antigens, Ly
  • Il15ra protein, mouse
  • Interleukin-15
  • Lectins, C-Type
  • Protein Subunits
  • Receptors, Immunologic
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2
  • Receptors, NK Cell Lectin-Like