Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow grafts

Nat Immunol. 2005 Sep;6(9):938-45. doi: 10.1038/ni1236. Epub 2005 Aug 7.

Abstract

Irradiation-resistant natural killer (NK) cells in an F(1) recipient can reject parental bone marrow, and host NK cells can also prevent engraftment of allogeneic bone marrow. We show here that repopulating bone marrow cells in certain mouse strains expressed retinoic acid early inducible 1 proteins, which are ligands for the activating NKG2D NK cell receptor. Treatment with a neutralizing antibody to NKG2D prevented rejection of parental BALB/c bone marrow in (C57BL/6 x BALB/c) F(1) recipients and allowed engraftment of allogeneic BALB.B bone marrow in C57BL/6 recipients. Additionally, bone marrow from C57BL/6 mice transgenic for retinoic acid early inducible 1epsilon was rejected by syngeneic mice but was accepted after treatment with antibody to NKG2D. If other stem cells or tissues upregulate expression of NKG2D ligands after transplantation, NKG2D may contribute to graft rejection in immunocompetent hosts.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation
  • Carrier Proteins / metabolism
  • Graft Rejection*
  • Histocompatibility Antigens Class I / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Ligands
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Minor Histocompatibility Antigens / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell

Substances

  • Antibodies, Monoclonal
  • Carrier Proteins
  • Histocompatibility Antigens Class I
  • Klrk1 protein, mouse
  • Ligands
  • Membrane Proteins
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily K
  • Raet1a protein, mouse
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • UL16 binding protein 1, mouse
  • minor H antigen H60