Novel murine autoimmune-mediated liver disease model induced by graft-versus-host reaction and concanavalin A.

Abstract

BACKGROUND AND AIMS:

We have previously reported that cluster of differentiation (CD)4+ T cells induced autoimmune liver diseases in mice with graft-versus-host reaction (GVHR) because of major histocompatibility complex (MHC) class II disparity. To analyze the progression of the autoimmune-related mechanism in the liver, concanavalin A (Con A) was injected in mice undergoing GVHR. The aim of this study is to clarify whether Con A deteriorates murine hepatic lesions induced by GVHR, and to elucidate the participation of the cytokines of liver-infiltrating CD4+ T cells.

METHODS:

Mice (F1; B6.C-H-2(bm12) x B6) were intravenously injected with B6 T spleen cells. Concanavalin A (15 mg/kg) was administrated 5 days after cell transfer. We examined serum transaminase, antimitochondrial antibodies (AMA), antinuclear antibodies (ANA) and histological changes. Liver-infiltrating CD4+ T cells were sorted and their cytokine mRNA expression was examined by the use of reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS:

Graft-versus-host reaction + Con A mice revealed an elevated serum transaminase, elevated AMA and ANA titers, increased periportal cellular infiltration, piecemeal necrosis and bridging necrosis in the liver. In this group, interferon (IFN)-gamma mRNA expression was more elevated than it was in the GVHR mice. However, there was no difference in the expression of interleukin (IL)-10 mRNA between the two groups.

CONCLUSION:

The results suggest that Con A deteriorates the GVHR-induced hepatic lesions, and IFN-gamma and IL-10 of CD4+ T cells might be implicated in the progression of autoimmune-related hepatic lesions. This model might offer an aspect for the investigation of progressive mechanisms in T-cell- mediated hepatobiliary injury.

• Authors: R Unno, Y Matsuzaki, S Itoh, M Doy, J Shoda, N Tanaka
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 16 Issue 10 Pg. 1149-57 (Oct 2001) ISSN: 0815-9319 [Print] Australia
• PMID: 11686843 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Cytokines
• RNA, Messenger
• Concanavalin A

Topics

• Analysis of Variance
• Animals
• Autoantibodies (analysis)
• Autoimmune Diseases (immunology, pathology)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Transplantation
• Concanavalin A (pharmacology)
• Cytokines (immunology)
• Disease Models, Animal
• Graft vs Host Disease (drug therapy, immunology, pathology)
• Hepatitis (immunology, pathology)
• Liver Function Tests
• Mice
• Mice, Inbred C57BL
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Spleen (immunology, pathology)