Abstracts (complete list) - Wissenschaft Online

Beatrice Bolinger, Philippe Krebs, Engeler Daniel, Ying Hua Tian, Elke Scandella,
Simone Miller, Nicola P. Restifo, Pierre-Alain Clavien, Burkhard Ludewig
Vascular endothelial cells presenting minor histocompatibility
antigen do neither activate nor tolerize CD8+ T cells
Endothelial cells (EC) are located at a unique position between circulating lymphocytes
and peripheral tissues and thereby participate in the recruitment of T lymphocytes from
the bloodstream to the sites of infection and inflammation. After transplantation of
vascularized allogeneic tissues, allopresentation by EC may contribute to allograft
rejection. However, the interaction between T cells and EC presenting a minor
histocompatibility antigen is still not fully understood. Using a transgenic mouse model
with β-galactosidase (βgal) expression confined to the vascular endothelium (Tie2-LacZ
mice) and mice with CD8+ T cells expressing a βgal-specific T cell receptor (Bg1 mice),
the role of EC during cognate interaction with CD8+ T cells was assessed in vivo.
Adoptive transfer of TCR transgenic Bg1 cells into naïve Tie2-LacZ recipients lead to
activation and proliferation of Bg1 CD8+ T cells. Generation of bone marrow chimeric
mice using mice which exhibit a mutated H2-Kb-molecule (bm1 mice) and impaired
presentation of Kb-restricted peptides, revealed that activation of βgal-specific CD8+ T
cells in Tie2-LacZ mice is mediated by bone marrow derived cells. In vivo depletion of
dendritic cells (DC) revealed that activation of CD8+ T cells in this setting depended
exclusively on cross-presentation by DC. Likewise, tolerization of TCR tg Bg1 cells was
not dependent on Ag presentation by vascular EC. The finding that the βgal antigen
expressed by vascular EC remains immunologically ignored by CTL in Tie2-LacZ mice
could be reproduced using heterotopic heart and orthotopic liver transplantation of Tie2-
LacZ organs into naïve C57BL/6 mice.Taken together, our results suggest that
presentation of a minor histocompatibility antigen by vascular EC leads neither to
activation nor to proliferation of specific CD8+ T cells.