An Inducible Transgenic Mouse Model for Immune Mediated Hepatitis Showing Clearance of Antigen Expressing Hepatocytes by CD8+ T Cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Pils, Marina C
MetadataShow full item record
AbstractThe liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA_X_CreER(T2) mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b)/OVA257-264-specific OT-I T cells to OVA_X_CreER(T2) mice or generated triple transgenic OVA_X CreER(T2)_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2) mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA_X_CreER(T2)_X_OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA_X_CreER(T2)_X_OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.
CitationAn Inducible Transgenic Mouse Model for Immune Mediated Hepatitis Showing Clearance of Antigen Expressing Hepatocytes by CD8+ T Cells. 2013, 8 (7):e68720 PLoS ONE
AffiliationModel Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Braunschweig, Germany.
The following license files are associated with this item:
- Differential priming of CD8 and CD4 T-cells in animal models of autoimmune hepatitis and cholangitis.
- Authors: Derkow K, Loddenkemper C, Mintern J, Kruse N, Klugewitz K, Berg T, Wiedenmann B, Ploegh HL, Schott E
- Issue date: 2007 Oct
- Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.
- Authors: Ochel A, Cebula M, Riehn M, Hillebrand U, Lipps C, Schirmbeck R, Hauser H, Wirth D
- Issue date: 2016 Nov
- Naive CD8 T-cells initiate spontaneous autoimmunity to a sequestered model antigen of the central nervous system.
- Authors: Na SY, Cao Y, Toben C, Nitschke L, Stadelmann C, Gold R, Schimpl A, Hünig T
- Issue date: 2008 Sep
- Aspergillus fumigatus extract differentially regulates antigen-specific CD4+ and CD8+ T cell responses to promote host immunity.
- Authors: Tao J, Segal BH, Eppolito C, Li Q, Dennis CG, Youn R, Shrikant PA
- Issue date: 2006 Sep
- Active CD4+ helper T cells directly stimulate CD8+ cytotoxic T lymphocyte responses in wild-type and MHC II gene knockout C57BL/6 mice and transgenic RIP-mOVA mice expressing islet beta-cell ovalbumin antigen leading to diabetes.
- Authors: Ye Z, Ahmed KA, Hao S, Zhang X, Xie Y, Munegowda MA, Meng Q, Chibbar R, Xiang J
- Issue date: 2008 Nov