Antigen - presentation by vascular endothelium : its role for CTL - mediated vascular injury

Wang, Xueya. Antigen - presentation by vascular endothelium : its role for CTL - mediated vascular injury. 2008, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_8496

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Background: EC express and present MHC class I restricted peptide antigens and due to the exposed position may be targeted by antigen-specific CTL. We wished to explore the type of vascular injury that is mediated by peptidespecific CTL in vivo when EC express the source protein from which the antigenic peptide is derived. Methods: We immunized mice that express E.coli -galactosidase (LacZ) as an antigen specifically under the control of the thrombomodulin promoter, i.e. in vascular endothelial cells, with -gal(500-507) pulsed dendritic cells. The peptide specific CTL-response was assessed in splenocytes by intracellular cytokine staining after peptide incubation and histopathological tissue sections were scrutinized for CTL-mediated EC injury. Results: After subcutaneous immunization, on average 1% of the CD8+ splenocytes were -gal-peptide specific effector cells. Despite of successful immunization we were unable to detect antigen-specific endothelial injury in TM-LacZ mice. A GVHD-like chronic inflammatory, antigen-specific disease characterized clinically by mild wasting was induced in ROSA26-LacZ mice, which ubiquitously express LacZ. Accidentally we observed persistent lung inflammatory infiltrates in mice that received intravenous injections of splenocytes or dendritic cells. These perivascular granuloma-like lesions consisted of highly proliferating CD11c+ recipient cells and were not the result of DC trapping. Conclusions: Endothelial cells escape CTL-mediated apoptosis in vivo. Intravenous injection of splenocytes and dendritic cells or both, leads to a model of pulmonary granuloma formation and this may represent an early stage of vasculitis.
Advisors:Dehio, Christoph
Committee Members:Biedermann, Barbara Claudia and Palmer, Ed
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Dehio, Christoph and Palmer, Ed
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:8496
Thesis status:Complete
Number of Pages:92
Identification Number:
edoc DOI:
Last Modified:22 Jan 2018 15:50
Deposited On:13 Feb 2009 16:52

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