HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen

Endothelial cells (ECs) presenting minor histocompatibility antigen (mhAg) are major target cells for alloreactive effector CD8 T cells during chronic transplant rejection and graft-versus-host disease (GVHD). The contribution of ECs to T-cell activation, however, is still a controversial issue. In this study, we have assessed the antigen-presenting capacity of ECs 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 ECs was not sufficient to either activate or tolerize CD8 T cells. Likewise, transplantation of fully vascularized heart or liver grafts from Tie2-LacZ mice into nontransgenic recipients did not suffice to activate -gal– specific CD8 T cells, indicating that CD8 T-cell responses against mhAg cannot be initiated by ECs. Moreover, we could show that spontaneous activation of -gal– specific CD8 T cells in Tie2-LacZ mice was exclusively dependent on CD11c dendritic cells (DCs), demonstrating that mhAgs presented by ECs remain immunologically ignored unless presentation by DCs is granted. (Blood. 2008;111: 4588-4595)