Cytokine profile of liver-infiltrating CD4(+) T cells separated from murine primary biliary cirrhosis-like hepatic lesions induced by graft-versus-host reaction

Background and Methods: We have previously reported that CD4(+) T cells ind uced primary biliary cirrhosis (PBC)-like hepatic lesions in mice with graf t-versus-host reaction due to major histocompatibility complex class II dis parity. To clarify the relationship between the cytokine profile produced b y CD4(+) T cells and the formation of hepatic lesions, we sorted CD4(+) T c ells from the liver by using flow cytometry and examined their cytokine mRN A expression at various times after GVHR induction. We also examined the as sociated changes in the serum levels of antimitochondrial antibodies (AMA). Results: Histologically, the infiltration of CD4(+) T cells around the bile ducts was observed from day 5, and the lesions deteriorated gradually unti l day 14. On day 14, CD8(+), B220(+) and Mac-1(+) cells, as well as CD4(+) T cells were seen around the bile ducts. In the liver-infiltrating CD4(+) T cells, the expression level of interferon-gamma (IFN-gamma) mRNA was obser ved to increase at an early phase (day 3), whereas that of interleukin (IL) -10 mRNA was elevated at a later phase (day 14). The elevation of IFN-gamma mRNA expression at an early phase before the appearance of non-suppurative destructive cholangitis suggests that IFN-gamma may be related to the path ogenesis of PBC in this model. Serum levels of AMA on day 14 were significa ntly higher than those on day 5. Interleukin-10 was considered to stimulate antibody production, to show an inhibitory effect upon the function of T h elper 1 cells, and to inhibit fibrosis. Conclusions: Interferon-gamma may play an important role in the pathogenesi s of this model. Moreover, delayed expression of IL-10 mRNA may control PBC -like hepatic lesions. (C) 2000 Blackwell Science Asia Pty Ltd.