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Novel murine autoimmune‐mediated liver disease model induced by graft‐versus‐host reaction and concanavalin A
Author(s) -
Unno Rie,
Matsuzaki Yasushi,
Itoh Shinichi,
Doy Mikio,
Shoda Junichi,
Tanaka Naomi
Publication year - 2001
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2001.02580.x
Subject(s) - concanavalin a , immunology , medicine , spleen , major histocompatibility complex , cytokine , autoimmune disease , mixed lymphocyte reaction , antibody , pathology , t cell , biology , antigen , immune system , biochemistry , in vitro
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 × 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)‐γ 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‐γ 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.