Submitted September 24, 2007
Accepted January 5, 2008
Immunological ignorance of vascular endothelial cells expressing minor histocompatibility antigen
Beatrice Bolinger, Philippe Krebs, Yinghua Tian, Daniel Engeler, Elke Scandella, Simone Miller, Douglas C. Palmer, Nicholas P. Restifo, Pierre-Alain Clavien, and Burkhard Ludewig*
Research Department, Kantonal Hospital St. Gallen, St. Gallen, Switzerland
Departement of Visceral Surgery, University Hospital Zurich, Zurich, Switzerland
National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: burkhard.ludewig{at}kssg.ch.
Endothelial cells (EC) presenting minor histocompatibility antigen (mhAg) are major target cells of alloreactive effector CD8+ T cells during chronic transplant rejection and graft-versus-host disease (GVHD). The contribution of EC to T cell activation, however, is still a controversial issue. In this study, we have assessed the antigen presenting capacity of EC in vivo using a transgenic mouse model with beta-galactosidase (
-gal) expression confined to the vascular endothelium (Tie2-LacZ mice). In a GVHD-like setting with adoptive transfer of -gal-specific T cell receptor transgenic T cells, -gal expression by EC was neither sufficient to activate nor to tolerize CD8+ T cells. Likewise, transplantation of fully vascularized heart or liver grafts from Tie2-LacZ mice into non-transgenic recipients did not suffice to activate -gal-specific CD8+ T cells, indicating that CD8+ T cell responses against mhAg cannot be initiated by EC. Moreover, we could show that spontaneous activation of -gal-specific CD8+ T cells in Tie2-LacZ mice was exclusively dependent on CD11c+ dendritic cells (DC) demonstrating that mhAg presented by EC remain immunologically ignored unless presentation by DC is granted.
