L3T4 + T cells induce hepatic lesions resembling primary biliary cirrhosis in mice with graft-versus-host reactions due to major histocompatibility complex class II disparity

Abstract

We had shown that the appearance of hepatic lesions such as epithelioid granulomas and chronic nonsuppurative destructive cholangitis (CNSDC)-like bile duct changes characteristic of primary biliary cirrhosis (PBC) in mice undergoing MHC class II-disparate graft-versus-host reactions (GVHR). To further examine the pathogenesis of the disease, we examined in the present study which T cell subset, i.e., L3T4 + or Lyt-2 + T lymphocytes, had an ability to induce such hepatic lesions. (B6 × bm12)F1 recipients were injected with unseparated T cells, L3T4 +, or Lyt-2 + T cells of B6 mice and on various days postinjection liver specimens were obtained. At Day 14 postinjection, livers of mice injected with whole T cells or L3T4 + T cells showed PBC-like histological changes, but none of the lesions were induced by Lyt-2 + T cells. Immunohistochemical studies revealed that Lyt-2 + as well as L3T4 + T cells were detected around bile ducts and some of them were infiltrating among bile duct epithelial cells. Kinetic studies showed that shortly after injection of L3T4 + T cells, L3T4 + T cells appeared around bile ducts and then Mac-1 + cells emerged. Lyt-2 + T cells and surface IgM + B cells were detected on Day 5 and increased thereafter. Hepatic granulomas consisted of both L3T4 + and Lyt-2 + T cells with a few B cells. The aberrant expression of MHC class II (Ia) antigen was detected mainly at the lateral surface of bile duct epithelial cells by Day 14 postinjection. Based on these findings, the developmental mechanism of PBC-like hepatic lesions induced in mice with GVHR was discussed.