This functional model of hepatocyte transplantation is validated for the study of host immune responses to hepatocellular grafts and to assess efficacy of strategies designed to alter these in vivo immune responses. The immunologic rejection of allogeneic hepatocytes appears to be T cell-mediated.

These studies show that both CD4+ and CD8+ T cells (but not host NTC) can independently initiate the rejection of allogeneic hepatocytes. While hepatocyte rejection by isolated CD4+ T cells is not surprising, rejection by CD8+ T cells (in the absence of CD4+ T cells) was unusual, and may explain the failure of "standard" immunosuppressive regimens to suppress acute rejection of allogeneic hepatocytes, as noted in prior studies. Furthermore, NK cells do not appear to be required for either CD4+ T cell or CD8+ T cell initiated hepatocyte rejection.

cInfluenza A virus infection can arrest autophagy, as evidenced by autophagosome accumulation in infected cells. Here, we report that this autophagosome accumulation can be inhibited by amantadine, an antiviral proton channel inhibitor, in amantadinesensitive virus infected cells or cells expressing influenza A virus matrix protein 2 (M2). Thus, M2 proton channel activity plays a role in blocking the fusion of autophagosomes with lysosomes, which might be a key mechanism for arresting autophagy.

Allogeneic hepatocytes introduced into the portal circulation via intrasplenic injection are immunogenic not tolerogenic and stimulate a weak humoral and strong cell mediated host immune response in vivo. Co-transplantation or pretransplantation of allogeneic liver NPCs did not protect allogeneic hepatocytes from immunologic rejection.