The transfer of host MHC class I protein protects donor cells from NK cell and macrophage-mediated rejection during hematopoietic stem cell transplantation and engraftment in mice

Authors

  • Theresa Chow,

    1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    2. Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Jennifer Whiteley,

    1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Search for more papers by this author
  • Mira Li,

    1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Search for more papers by this author
  • Ian M. Rogers

    Corresponding author
    1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    2. Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    3. Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
    • Correspondence: Ian M. Rogers, Ph.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. Telephone: 416-586-4800, ext. 4122; Fax: 416-586-5130; e-mail: rogers@lunenfeld.ca

    Search for more papers by this author

  • Author contributions:. T.C.: performed experiments, analyzed data, designed experiments, and wrote manuscript; J.W. and M.L.: performed experiments; I.M.R.: designed experiments, analyzed data, and wrote manuscript.

Abstract

Human hematopoietic stem cell engraftment has been studied extensively using xenograft transplant models with immunocompromised mice. It is standard practice to incorporate mouse models, such as the limiting dilution assay, to accurately assess the number of repopulating stem cells in bone marrow or umbilical cord blood collections or to confirm the long-term repopulating ability of cultured hematopoietic stem cells. In a previous study using a standard NOD/SCID mouse model to assess human hematopoietic stem cell engraftment we observed that all human cells had mouse MHC class I protein on their surface, suggesting that this is a mechanism adopted by the cells to evade host immune surveillance. To determine whether this was a xenograft phenomenon we studied host MHC transfer in an intraspecies mouse model and observed similar results. The transfer of MHC class I proteins has implications for antigen presentation and immune modulation. In this report, we used a standard mouse model of bone marrow transplantation to demonstrate that surface protein transfer between cells plays an important role in protecting donor hematopoietic cells from NK cell and macrophage-mediated rejection. The transfer of intact MHC class I antigens from host cells to transplanted donor cells confers a self identity on these otherwise foreign cells. This gives them the ability to evade detection by the host NK cells and macrophages. Once full donor chimerism is established, transplanted cells no longer require host MHC class I protein transfer to survive. Stem Cells 2013;31:2242–2252

Ancillary