Mouse host unlicensed NK cells promote donor allogeneic bone marrow engraftment

Blood. 2016 Mar 3;127(9):1202-5. doi: 10.1182/blood-2015-08-665570. Epub 2016 Jan 6.

Abstract

Natural killer (NK) cells exist as subsets based on expression of inhibitory receptors that recognize major histocompatibility complex I (MHCI) molecules. NK cell subsets bearing MHCI binding receptors for self-MHCI have been termed as "licensed" and exhibit a higher ability to respond to stimuli. In the context of bone marrow transplantation (BMT), host licensed-NK (L-NK) cells have also been demonstrated to be responsible for the acute rejection of allogeneic and MHCI-deficient BM cells (BMCs) in mice after lethal irradiation. However, the role of recipient unlicensed-NK (U-NK) cells has not been well established with regard to allogeneic BMC resistance. After NK cell stimulation, the prior depletion of host L-NK cells resulted in a marked increase of donor engraftment compared with the untreated group. Surprisingly, this increased donor engraftment was reduced after total host NK cell depletion, indicating that U-NK cells can actually promote donor allogeneic BMC engraftment. Furthermore, direct coculture of U-NK cells with allogeneic but not syngeneic BMCs resulted in increased colony-forming unit cell growth in vitro, which was at least partially mediated by granulocyte macrophage colony-stimulating factor (GM-CSF) production. These data demonstrate that host NK cell subsets exert markedly different roles in allogeneic BMC engraftment where host L- and U-NK cells reject or promote donor allogeneic BMC engraftment, respectively.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow Transplantation*
  • Female
  • Histocompatibility Antigens Class I / metabolism
  • Killer Cells, Natural / immunology*
  • Macrophage Colony-Stimulating Factor / biosynthesis
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Transplantation, Homologous

Substances

  • Histocompatibility Antigens Class I
  • Macrophage Colony-Stimulating Factor
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Ptpn6 protein, mouse