Protective role of gamma interferon during the recall response to influenza virus.
During secondary immune responses to influenza virus, virus-specific T memory cells are a major source of gamma interferon (IFN-gamma). We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68 (H3N2) virus. The IFN-gamma-/- mice displayed significantly reduced survival rates subsequent to a challenge with various doses of the A/WSN/33 virus. This was associated with an impaired ability of the IFN-gamma-/- mice to completely clear the pulmonary virus by day 7 after the challenge, although significant reduction of the virus titers was noted. However, the IFN-gamma-/- mice developed type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution assay for the estimation of CTL precursor frequency. The pulmonary recruitment of T cells in IFN-gamma-/- mice was not dramatically affected, and the percentage of CD4(+) and CD8(+) T cells was similar to that of wild-type mice. The T cells from IFN-gamma-/- mice did not display a significant switch toward a Th2 profile. Furthermore, the IFN-gamma-/- mice retained the ability to mount significant titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies. Together, these results are consistent with a protective role of IFN-gamma during the heterologous response against influenza virus independently of the generation and local recruitment of cross-reactive CTLs.
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Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA. ABot@allp.com
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D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002417:Cattle; D002460:Cell Line; D003429:Cross Reactions; D004195:Disease Models, Animal; D004285:Dogs; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009500:Neutralization Tests; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma