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


CONCLUSIONS
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.
Unno
R
R
Division of Gastroenterology and Hepatology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Matsuzaki
Y
Y
Itoh
S
S
Doy
M
M
Shoda
J
J
Tanaka
N
N
D000704:Analysis of Variance; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017690:Cell Transplantation; D003208:Concanavalin A / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology; D008111:Liver Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger; D003208:Concanavalin A