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 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.
Department of Surgery, University of Pennsylvania Health System, Philadelphia 19104, USA.
Daniel
D
Kreisel
Alyssa M
AM
Krasinskas
Alexander S
AS
Krupnick
Andrew E
AE
Gelman
Keki R
KR
Balsara
Sicco H
SH
Popma
Markus
M
Riha
Ariella M
AM
Rosengard
Laurence A
LA
Turka
Bruce R
BR
Rosengard
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II