Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-7968
Bolinger, B; Krebs, P; Tian, Y; Engeler, D; Scandella, E; Miller, S; Palmer, D C; Restifo, N P; Clavien, P A; Ludewig, B (2008). Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen. Blood, 111(9):4588-4595.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery|
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
|DDC:||610 Medicine & health|
|Deposited On:||11 Dec 2008 15:38|
|Last Modified:||23 Nov 2012 16:23|
|Publisher:||American Society of Hematology|
|Additional Information:||This research was originally published in Blood, 2008; 111(9). Copyright by the American Society of Hematology.|
|WoS Citation Count:||6|
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