Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen Presentation
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Antigen-Presenting Cells / immunology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Coculture Techniques
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Endothelium, Vascular / cytology
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Endothelium, Vascular / immunology*
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Endothelium, Vascular / physiology
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Graft Rejection / immunology*
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Graft Rejection / physiopathology
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Heart Transplantation / immunology*
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Histocompatibility Antigens / immunology
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Humans
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In Situ Nick-End Labeling
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Interferon-gamma / metabolism
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Interleukin-2 / metabolism
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Interleukin-4 / metabolism
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Isoantigens / immunology
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Lymphocyte Activation / immunology*
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Lymphocyte Activation / physiology
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Male
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Mice
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Mice, Inbred Strains
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Mice, Transgenic
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Myocardium / pathology
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Spleen / cytology
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Transplantation Chimera
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Transplantation, Homologous / immunology*
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Transplantation, Homologous / physiology
Substances
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Histocompatibility Antigens
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Interleukin-2
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Isoantigens
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Interleukin-4
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Interferon-gamma