Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: an alternative mechanism of allorecognition

Nat Med. 2002 Mar;8(3):233-9. doi: 10.1038/nm0302-233.


Despite evidence that human non-hematopoietic cells, such as vascular endothelium, can activate allogeneic T lymphocytes in vitro, the prevailing view has been that hematopoietic antigen-presenting cells are required to trigger alloimmune responses in vivo. Here we report that mouse non-hematopoietic cells activate alloreactive CD8+ T lymphocytes in vitro and in vivo. We also show that vascularized cardiac allografts are acutely rejected via CD8+ direct allorecognition even if the alloantigen is not presented by hematopoietic professional antigen-presenting cells. Because activation of alloreactive CD8+ T cells by donor-type non-hematopoietic cells can continue for the life of the allograft, these findings present a new clinically relevant mechanism of allorecognition and should be taken into consideration when developing strategies to prevent allograft vasculopathy or to induce tolerance.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / physiology
  • Graft Rejection / immunology*
  • Graft Rejection / physiopathology
  • Heart Transplantation / immunology*
  • Histocompatibility Antigens / immunology
  • Humans
  • In Situ Nick-End Labeling
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Isoantigens / immunology
  • Lymphocyte Activation / immunology*
  • Lymphocyte Activation / physiology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Myocardium / pathology
  • Spleen / cytology
  • Transplantation Chimera
  • Transplantation, Homologous / immunology*
  • Transplantation, Homologous / physiology


  • Histocompatibility Antigens
  • Interleukin-2
  • Isoantigens
  • Interleukin-4
  • Interferon-gamma