Neutrophils mediate parenchymal tissue necrosis and accelerate the rejection of complete major histocompatibility complex-disparate cardiac allografts in the absence of interferon-γ

A major feature of acute rejection of cardiac allografts; is an intense mononuclear cell infiltration accompanied by interferon (ILFN)-gamma production. in the current study we tested the role of IFN-gamma in acute rejection of allografts by comparing the histopathology of rejection in wildtype versus IFN-y(-/-) recipients. of major histocompatibility complex-mismatched cardiac grafts. Wild-type recipients rejected the allografts at days 8 to 9 after transplant but rejection was accelerated 2 to 3 days in IFN-gamma-deficient recipients. During rejection in wildtype recipients, the allografts were heavily infiltrated with CD8(+) T cells and other mononuclear cells. in contrast, allografts in IFN-gamma-deficient recipients had few T cells but an intense neutrophil infiltration accompanied by extensive graft parenchymal necrosis. No difference in expression levels of neutrophil chemoattractants including Groalpha/KC, MIP-2, GCP-2, and MIP-1alpha, was observed in allografts retrieved from wild-type and IFN-y(-/-) recipients. Depletion of neutrophils from IFN-gamma-deficient recipients delayed rejection until days 8 to 10 after transplant and restored the histopathology of acute allograft rejection to that observed in allografts; rejected by wild-type recipients. These results indicate the potent regulatory properties of IFN-gamma during acute rejection directed at neutrophil infiltration into allografts; and mediating graft tissue necrosis.