| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1-Deficient Mice Develop Necroinflammatory IFN-
-Dependent Hepatitis1
Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756
Autoimmune hepatitis (AIH) in humans arises spontaneously in
genetically susceptible individuals and is associated with the presence
of Th1 cells in the liver. The understanding of AIH has advanced more
slowly than that of other organ-specific autoimmune diseases, however,
largely because of the lack of an appropriate animal model. We now
describe a new mouse model characterized by spontaneous development of
necroinflammatory hepatitis that is restricted by genetic background.
Mice deficient in the immunomodulatory cytokine TGF-
1 were
extensively back-bred to the BALB/c background. The BALB/c background
dramatically modified the phenotype of TGF-1-/- mice:
specifically, BALB/c-TGF-1-/- mice developed a lethal
necroinflammatory hepatitis that was not observed in
TGF-1-/- mice on a different genetic background.
BALB/c background TGF-1-/- livers contained large
numbers of activated CD4+ T cells that produced large
quantities of IFN-
, but little IL-4, identifying them as Th1 cells.
BALB/c background TGF-1-/-/IFN--/-
double knockout mice, generated by cross-breeding, did not develop
necroinflammatory hepatitis, demonstrating that IFN- is
mechanistically required for its pathogenesis. This represents the
first murine model of hepatitis that develops spontaneously, is
restricted by genetic background, and is dependent upon the Th1
cytokine IFN-, and that thus recapitulates these important aspects
of AIH.
This article has been cited by other articles:
|
|
 |
|
  S. Perruche, P. Zhang, T. Maruyama, J. A. Bluestone, P. Saas, and W. Chen Lethal Effect of CD3-Specific Antibody in Mice Deficient in TGF-{beta}1 by Uncontrolled Flu-Like Syndrome J. Immunol., July 15, 2009; 183(2): 953 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vitsky, J. Waire, R. Pawliuk, A. Bond, D. Matthews, E. LaCasse, M. L. Hawes, C. Nelson, S. Richards, P. A. Piepenhagen, et al. Homeostatic Role of Transforming Growth Factor-{beta} in the Oral Cavity and Esophagus of Mice and Its Expression by Mast Cells in These Tissues Am. J. Pathol., June 1, 2009; 174(6): 2137 - 2149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Robinson, J. Wang, J. G. Cripps, M. W. Milks, K. A. English, T. A. Pearson, and J. D. Gorham End-Organ Damage in a Mouse Model of Fulminant Liver Inflammation Requires CD4+ T Cell Production of IFN-{gamma} but Is Independent of Fas J. Immunol., March 1, 2009; 182(5): 3278 - 3284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Robinson and J. D. Gorham TGF-beta1 Regulates Antigen-Specific CD4+ T Cell Responses in the Periphery J. Immunol., July 1, 2007; 179(1): 71 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I.-K. Park, L. D. Shultz, J. J. Letterio, and J. D. Gorham TGF-{beta}1 Inhibits T-bet Induction by IFN-{gamma} in Murine CD4+ T Cells through the Protein Tyrosine Phosphatase Src Homology Region 2 Domain-Containing Phosphatase-1 J. Immunol., November 1, 2005; 175(9): 5666 - 5674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Lin, S. L. Martin, L. Xia, and J. D. Gorham TGF-{beta}1 Uses Distinct Mechanisms to Inhibit IFN-{gamma} Expression in CD4+ T Cells at Priming and at Recall: Differential Involvement of Stat4 and T-bet J. Immunol., May 15, 2005; 174(10): 5950 - 5958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-H. Kim, F. Hong, S. Radaeva, B. Jaruga, S. Fan, and B. Gao STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury Am J Physiol Gastrointest Liver Physiol, October 1, 2003; 285(4): G761 - G768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bommireddy, V. Saxena, I. Ormsby, M. Yin, G. P. Boivin, G. F. Babcock, R. R. Singh, and T. Doetschman TGF-{beta}1 Regulates Lymphocyte Homeostasis by Preventing Activation and Subsequent Apoptosis of Peripheral Lymphocytes J. Immunol., May 1, 2003; 170(9): 4612 - 4622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Rudner, J. T. Lin, I.-K. Park, J. M. M. Cates, D. A. Dyer, D. M. Franz, M. A. French, E. M. Duncan, H. D. White, and J. D. Gorham Necroinflammatory Liver Disease in BALB/c Background, TGF-{beta}1-Deficient Mice Requires CD4+ T Cells J. Immunol., May 1, 2003; 170(9): 4785 - 4792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bommireddy, I. Ormsby, M. Yin, G. P. Boivin, G. F. Babcock, and T. Doetschman TGF{beta}1 Inhibits Ca2+-Calcineurin-Mediated Activation in Thymocytes J. Immunol., April 1, 2003; 170(7): 3645 - 3652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schramm, M. Protschka, H. H. Kohler, J. Podlech, M. J. Reddehase, P. Schirmacher, P. R. Galle, A. W. Lohse, and M. Blessing Impairment of TGF-beta signaling in T cells increases susceptibility to experimental autoimmune hepatitis in mice Am J Physiol Gastrointest Liver Physiol, March 1, 2003; 284(3): G525 - G535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Djilali-Saiah, P. Lapierre, S. Vittozi, and F. Alvarez DNA Vaccination Breaks Tolerance for a Neo-Self Antigen in Liver: A Transgenic Murine Model of Autoimmune Hepatitis J. Immunol., November 1, 2002; 169(9): 4889 - 4896. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
