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Hypercytokinemia has been considered to be responsible for hemophagocytosis and multiorgan failure in severe human cases of H5N1 viral infection. In this study, we show a recombinant hemagglutinin (H5) from a H5N1 virus may suppress the perforin expression and reduce cytotoxicity of human CD8+ T cells to kill H5-bearing cells. The persistence of H5-presenting cells provides sustained stimulation and leads to a marked lymphoproliferation and IFN-gamma hyperproduction. We propose the IFN-gamma hyperproduction may explain macrophage overactivation and subsequent hypercytokinemia and hemophagocytosis in severe human cases of avian influenza.

Cutting Edge: Insufficient Perforin Expression in CD8+ T Cells in Response to Hemagglutinin from Avian Influenza (H5N1) Virus