Previously, we demonstrated that purified hepatocytes (in the absence of donor-type antigen-presenting cells) are immunogenic in vitro in mixed lymphocyte hepatocyte culture (MLHC) by virtue of expression of major histocompatibility complex (MHC) class I. 1-5 Tumor necrosis factor ␣ (TNF-␣) is an inflammatory cytokine known to up-regulate MHC class I and adhesion molecule expression, and has been demonstrated to be important in the rejection of vascularized organ allografts. [6][7][8] In some models, host treatment with a monoclonal antibody directed against this cytokine prolongs graft survival of rat cardiac, liver, and renal allografts. 6-12 However, the mechanism by which immunotherapy directed against this cytokine influences graft survival is unknown.Adhesion molecules (intercellular adhesion molecule-1 [ICAM-1] and vascular cell adhesion molecule-1 [VCAM-1]) also appear to play important roles in vascularized organ allograft rejection since monoclonal antibodies directed against ICAM-1 and VCAM-1 have been shown to be effective in prolonging graft survival of murine cardiac allografts, cynomologous monkey renal transplants, and human renal transplants. [13][14][15][16][17] ICAM-1 has been implicated in liver transplant rejection by studies that show increased levels of soluble ICAM-1 during rejection episodes and histological detection of increased ICAM-1 expression during liver allograft rejection. Parenchymal cells (including liver cells) may constitutively express or may be induced to express adhesion molecules by various cytokines. However, the role of adhesion molecules in the presentation of MHC antigens by parenchymal cells is not known. Cytokines, including interleukin-1, interferon gamma, and TNF-␣, have been shown to up-regulate hepatocyte expression of ICAM-1 and their adhesion to T lymphocytes in vitro. 18 However, the in vivo effects of various cytokines on adhesion molecule expression in the liver has not been described, and the consequences of in vivo cytokine exposure on the immunogenicity of liver cells has not been studied. The current studies were undertaken to determine the effect of the inflammatory cytokine Abbreviations: MLHC, mixed lymphocyte hepatocyte culture; MHC, major histocompatibility complex; TNF-␣, tumor necrosis factor ␣; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; HC, hepatocyte; NPC, nonparenchymal cell; FBS, fetal bovine serum; MLNPC, mixed lymphocyte nonparenchymal cell culture; cpm, counts per minute; E:T, effector-to-target; GART-FITC, goat-anti-rat-fluorescein isothiocyanate conjugated; MFI, mean fluorescent intensity; allo-CTL, allospecific cytotoxic T lymphocyte; SMA, sponge matrix allograft.From the