Publikation

Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen

Wissenschaftlicher Artikel/Review - 01.05.2008

Bereiche
PubMed
DOI

Zitation
Bolinger B, Clavien P, Restifo N, Palmer D, Miller S, Scandella E, Engeler D, Tian Y, Krebs P, Ludewig B. Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen. Blood 2008; 111:4588-95.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Blood 2008; 111
Veröffentlichungsdatum
01.05.2008
eISSN (Online)
1528-0020
Seiten
4588-95
Kurzbeschreibung/Zielsetzung

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 (beta-gal) expression confined to the vascular endothelium (Tie2-LacZ mice). In a GVHD-like setting with adoptive transfer of beta-gal-specific T-cell receptor-transgenic T cells, beta-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 beta-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 beta-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.