Role of natural killer cell subsets in cardiac allograft rejection

Am J Transplant. 2006 Mar;6(3):505-13. doi: 10.1111/j.1600-6143.2005.01226.x.


To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4(+) T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8(+) T cells and NK1.1(+) cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2(+) NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Proliferation
  • Disease Models, Animal
  • Genes, MHC Class I / immunology
  • Graft Rejection / immunology*
  • Graft Rejection / metabolism
  • Graft Rejection / pathology
  • Heart Transplantation / immunology*
  • Immune Tolerance / immunology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell
  • Transplantation, Homologous


  • Antigens, Ly
  • Klrk1 protein, mouse
  • Ly49G2 receptor
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell