Insufficient perforin expression in CD8+ T cells in response to hemagglutinin from avian influenza (H5N1) virus.

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.