Liver T cell subsets and adhesion molecules in murine graft-versus-host disease

Murine GVHD across multiple minor histocompatibility barriers (B10.D2 into irradiated BALB/c) results in cell-mediated destruction of bile ducts inside the liver. Similar changes are characteristic of hepatic GVHD in humans following BMT. We have defined the phenotypes of inflammatory cells and the accessory/adhesion molecules expressed in the liver between day 7-14 of murine GVHD. T cells (CD3+) comprised 65% of hepatic inflammatory cells. alpha-beta and gamma-delta cells accounted for 92 and 8%, respectively of hepatic T cells. The percentage of CD4+ cells (29%) was 3 times that of CD8+ cells (11%). Lymphocyte function-associated antigen-1 (LFA-1) was expressed by the majority of inflammatory cells. Thirty per cent of the cells were positive for Mac-1, a differentiation marker of macrophages, large granular lymphocytes, and natural killer cells. Expression of intercellular adhesion molecule-1 and major histocompatibility complex class II (IAd) molecules on bile duct epithelial and portal vein endothelial cells was induced during GVHD. These results suggest that hepatic GVHD is induced by donor alpha-beta T cells through mechanisms that may involve CD4:1Ad and LFA-1:ICAM-1 interactions.