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

Abstract

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. 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). 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. 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.