Enhanced antibody and cytokine responses to influenza viral antigens in perforin-deficient mice.
Cytotoxic T lymphocytes (CTL) lyse virus-infected target cells by secreting 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, perforin-deficient mice generated about 100-fold greater serum antibody responses than wild-type mice. Further, immune spleen cells from perforin knock-out mice secreted over 10-fold more IFN-gamma following in vitro restimulation than immune spleen cells from control mice. Finally, 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, these results suggest that perforin-mediated effector function is required in the down-regulation of the immune response by way of limiting antigen-presenting cell function.
Sambhara
S
S
Pàsteur Mérieux Connaught Canada, Research Centre, North York, Ontario, Canada.
Switzer
I
I
Kurichh
A
A
Miranda
R
R
Urbanczyk
L
L
James
O
O
Underdown
B
B
Klein
M
M
Burt
D
D
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage*; D016207:Cytokines / Q000096:biosynthesis*; D016882:ISCOMs / Q000008:administration & dosage; D007114:Immunization; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage
D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D016882:ISCOMs; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014765:Viral Vaccines; D054353:Perforin; D007371:Interferon-gamma