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- Title
Systemic minor histocompatibility antigen expression in blood endothelial cells prevents T cell-mediated vascular immunopathology.
- Authors
Caviezel‐Firner, Sonja; Engeler, Daniel; Bolinger, Beatrice; Onder, Lucas; Scandella, Elke; Yu, Meimei; Kroczek, Richard. A.; Ludewig, Burkhard
- Abstract
Attenuation of T cell-mediated damage of blood endothelial cells ( BECs) in transplanted organs is important to prevent transplant vasculopathy ( TV) and chronic rejection. Here, we assessed the importance of minor histocompatibility antigen (m HA) distribution and different coinhibitory molecules for T cell- BEC interaction. A transgenic m HA was directed specifically to BECs using the Tie2 promoter and cellular interactions were assessed in graft-versus-host disease-like and heterotopic heart transplantation settings. We found that cognate CD4+ T-cell help was critical for the activation of BEC-specific CD8+ T cells. However, systemic m HA expression on BECs efficiently attenuated adoptively transferred, BEC-specific CD4+ and CD8+ T cells and hence prevented tissue damage, whereas restriction of m HA expression to heart BECs precipitated the development of TV. Importantly, the lack of the coinhibitory molecules programed death-1 ( PD-1) and B and T lymphocyte attenuator fostered the initial activation of BEC-specific CD4+ T cells, but did not affect development of TV. In contrast, TV was significantly augmented in the absence of PD-1 on BEC-specific CD8+ T cells. Taken together, these results indicate that antigen distribution in the vascular bed determines the impact of coinhibition and, as a consequence, critically impinges on T cell-mediated vascular immunopathology.
- Publication
European Journal of Immunology, 2013, Vol 43, Issue 12, p3233
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201343545