Vascular Endothelium Does Not Activate CD4+ Direct Allorecognition in Graft Rejection

Expression of MHC class II by donor-derived APCs has been shown to be important for allograft rejection. It remains controversial, however, whether nonhemopoietic cells, such as vascular endothelium, possess Ag-presenting capacity to activate alloreactive CD4(+) T lymphocytes. This issue is importan...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-09, Vol.173 (5), p.3027-3034
Main Authors: Kreisel, Daniel, Krasinskas, Alyssa M, Krupnick, Alexander S, Gelman, Andrew E, Balsara, Keki R, Popma, Sicco H, Riha, Markus, Rosengard, Ariella M, Turka, Laurence A, Rosengard, Bruce R
Format: Article
Language:English
Subjects:
Animals
Antigen-Presenting Cells - immunology
CD4 Antigens - immunology
Endothelium, Vascular - immunology
Graft Rejection - immunology
Heart Transplantation - immunology
Histocompatibility Antigens Class II - immunology
In Vitro Techniques
Male
Mice
Mice, Inbred C57BL
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Summary:Expression of MHC class II by donor-derived APCs has been shown to be important for allograft rejection. It remains controversial, however, whether nonhemopoietic cells, such as vascular endothelium, possess Ag-presenting capacity to activate alloreactive CD4(+) T lymphocytes. This issue is important in transplantation, because, unlike hemopoietic APCs, allogeneic vascular endothelium remains present for the life of the organ. In this study we report that cytokine-activated vascular endothelial cells are poor APCs for allogeneic CD4(+) T lymphocytes in vitro and in vivo despite surface expression of MHC class II. Our in vitro observations were extended to an in vivo model of allograft rejection. We have separated the allostimulatory capacity of endothelium from that of hemopoietic APCs by using bone marrow chimeras. Hearts that express MHC class II on hemopoietic APCs are acutely rejected in a mean of 7 days regardless of the expression of MHC class II on graft endothelium. Alternatively, hearts that lack MHC class II on hemopoietic APCs are acutely rejected at a significantly delayed tempo regardless of the expression of MHC class II on graft endothelium. Our data suggest that vascular endothelium does not play an important role in CD4(+) direct allorecognition and thus does not contribute to the vigor of acute rejection.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.173.5.3027