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Lessons from animal models of primary biliary cirrhosis

transplantation has been reported. The GVHD model promises a better understanding of the aetiology of PBC and may have important advantages over competing models for the treatment of this disease. It has been reported that alloreactive T cells that respond directly to foreign major histocompatibility complex (MHC) molecules and bound peptides play a central role in GVHD and allograft rejection. It has been also reported that the clinical manifestations observed in the GVHD animal model correlate with the profile of lymphokines produced by donor T cells activated in the spleen. In this issue, Itoh et al. report that CD4 T cells induced PBC-like hepatic lesions in mice with GVHD because of MHC class disparity. In this model, anti-mitochondrial antibodies (AMA) became positive and non-suppurative destructive cholangitis, which is a histological feature of PBC, was clearly observed. Furthermore, they found that these changes were induced in a two-stage manner. In the early stage (day 3), the expression level of interferon (IFN)-gmRNA increased, whereas in the late stage (after 14 days) that of interleukin (IL)-10 mRNA increased. They also reported that IFN-g-mRNA expression preceded the appearance of non-suppurative destructive cholangitis, indicating that IFN-g may play an important pathogenic role in this animal model. They also speculated that late-phase elevation of IL-10 may be related to auto-antibody formation. These findings may lead to the next step in understanding the immunopathophysiology of PBC and may result in a cytokine-related therapeutic strategy through regulation of the immune responses implicated in the progress of PBC. It is noteworthy that Itoh et al. identified at least two stages involved in the initial event of this model. Unfortunately, their model did not document fibrotic change or a chronic condition. While it is important to acknowledge that there are probably many different factors involved in the human disease, new knowledge about immune responses involving the cytokine network are certainly of value in furthering our understanding of PBC. See article on page 443