An immunohistological study of human hepatic graft-versus-host disease

Using immunohistological techniques, leucocytes were enumerated in portal tracts and bile duct epithelium in bone marrow transplant recipients with and without evidence of hepatic graft versus host disease (GvHD) and compared with normal subjects. Samples were obtained 8-169 days after transplantation. In marrow recipients without graft versus host disease (GvHD), inducer and suppressor/cytotoxic lymphocytes were reduced in number in the portal tracts compared with normal subjects. In GvHD, suppressor/cytotoxic lymphocytes were increased relative to non-GvHD recipients, but did not exceed normal values, while inducer cell numbers remained low. Natural killer cells (HNK1+) were not found in normal subjects, were present in small numbers in non-GvHD transplant cases and significantly increased in GvHD. The total number of portal tract leucocytes was not elevated in GvHD and the changes in the relative proportions of cells were similar to those that have been observed in the peripheral blood after transplantation. There was no increase in the number of lymphocytes expressing the activation markers Tac, T10 and HLA-DR nor in the number of leucocytes within the bile duct epithelium itself. These findings differ from those we have previously obtained in a similarly treated group of patients with cutaneous GvHD where lymphocytes were increased in the epithelium and stroma and expressed activation markers. Like the epidermis of the skin, however, the bile duct epithelium showed increased staining for HLA-DR antigens in all cases, but focal staining was also present in four of the seven marrow recipients without GvHD. The significance of these findings is discussed.