Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-10876
Voehringer, D; Blaser, C; Grawitz, A B; Chisari, F V; Buerki, K; Pircher, H (2000). Break of T cell ignorance to a viral antigen in the liver induces hepatitis. Journal of Immunology, 165(5):2415-2422.
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To study peripheral tolerance of CD8 T cells to a classically MHC-restricted peptide Ag expressed in hepatocytes, ALB1 transgenic (tg) mice expressing the CTL epitope GP33 of the lymphocytic choriomeningitis virus glycoprotein under control of the mouse albumin promoter were generated. ALB1 mice exclusively expressed the GP33 transgene in the liver and, at a 100- to 1000-fold lower level, in the thymus. TCR-tg mice specific for the GP33 epitope were used to directly follow GP33-specific T cells in vivo. These experiments revealed that 1) thymic expression of the GP33 transgene led to incomplete central deletion of TCR-tg cells; and 2) peripheral TCR-tg cells in ALB1 mice ignored the GP33 transgene expressed in hepatocytes. Ignorance of adoptively transferred TCR-tg cells in ALB1 mice was broken by infection with lymphocytic choriomeningitis virus, leading to induction of hepatitis in ALB1, but not in control, mice. Taken together, we have established a novel model of virus-induced CD8 T cell-mediated autoimmune hepatitis in mice and demonstrate that naive CD8 T cells may ignore Ags expressed in the liver.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Laboratory Animal Science|
04 Faculty of Medicine > Institute of Laboratory Animal Science
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||25 Mar 2009 07:20|
|Last Modified:||27 Nov 2013 23:38|
|Publisher:||American Association of Immunologists|
|Free access at:||PubMed ID. An embargo period may apply.|
|Citations:||Web of Science®. Times cited: 53|
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