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 (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.
Bolinger
Beatrice
B
Research Department, Kantonal Hospital, St Gallen, Switzerland.
Krebs
Philippe
P
Tian
Yinghua
Y
Engeler
Daniel
D
Scandella
Elke
E
Miller
Simone
S
Palmer
Douglas C
DC
Restifo
Nicholas P
NP
Clavien
Pierre-Alain
PA
Ludewig
Burkhard
B
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000032:analysis* / Q000276:immunology; D016377:Organ Transplantation / Q000009:adverse effects; D014181:Transplantation Immunology
D015778:Minor Histocompatibility Antigens