Interferon-gamma gene expression during acute graft-versus-host disease: Relationship to MHC induction and tissue injury

The pathogenetic role of interferon-γ (IFN-γ) in acute graft-versus- host disease (GVHD) was examined in a murine model. IFN-γ gene expression was evaluated by northern blotting and mRNA in situ hybridization. The temporal and tissue specific patterns of IFN-γ gene expression were related to the patterns of major histocompatibility complex (MHC) antigen induction and of tissue injury. Markedly increased levels of IFN-γ transcripts were seen in the spleen during the early lymphoproliferative phase and coincided with widespread MHC induction in non-lymphoid tissues. Increased IFN-γ transcripts were also found in the non-lymphoid target tissues during the phase of subsequent tissue injury. These findings support a role for IFN-γ in leading to widespread MHC induction during acute GVHD and suggest that IFN-γ may also contribute to target tissue injury during acute GVHD.