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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4588-4595.
Prepublished online as a Blood First Edition Paper on January 14, 2008; DOI 10.1182/blood-2007-09-114769.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen

Beatrice Bolinger1,*, Philippe Krebs1,*, Yinghua Tian2, Daniel Engeler1, Elke Scandella1, Simone Miller1, Douglas C. Palmer3, Nicholas P. Restifo3, Pierre-Alain Clavien2, and Burkhard Ludewig1

1 Research Department, Kantonal Hospital, St Gallen, Switzerland; 2 Departement of Visceral Surgery, University Hospital Zurich, Zurich, Switzerland; and 3 National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD

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


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Related Article in Blood Online:

Ignorance is bliss
Daniel Zecher and Fadi G. Lakkis
Blood 2008 111: 4426-4427. [Full Text] [PDF]





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