ENHANCED ANTIBODY AND CYTOKINE RESPONSES TO INFLUENZA VIRAL-ANTIGENS IN PERFORIN-DEFICIENT MICE

Cytotoxic T lymphocytes (CTL) lyse virus-infected target cells by secr eting the pore-forming effector molecule, perforin. Perforin-mediated cell death appears to be a major mechanism in viral clearance but its role in regulating immune responses in vivo is unclear. In this report , we show that following immunization with influenza viral antigens, p erforin-deficient mice generated about 100-fold greater serum antibody responses than wild-type mice. Further, immune spleen cells from perf orin knock-out mice secreted over 10-fold more IFN-gamma following in vitro restimulation than immune spleen cells from control mice. Finall y, there were over 10-fold more IFN-gamma-secreting cells in cultures from perforin-deficient mice than those from control mice, suggesting that the enhanced cytokine release by T cells from perforin-deficient mice is due to an increase in the effector cell pool. Collectively, th ese results suggest that perforin-mediated effector function is requir ed in the down-regulation of the immune response by way of limiting an tigen-presenting cell function. (C) 1998 Academic Press.