Gamma interferon is not required for mucosal cytotoxic T-lymphocyte responses or heterosubtypic immunity to influenza A virus infection in mice. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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Gamma interferon is not required for mucosal cytotoxic T-lymphocyte responses or heterosubtypic immunity to influenza A virus infection in mice.

J Virol. 2000 Jun;74(12):5495-501. Unique Identifier : AIDSLINE MED/20283806
Nguyen HH; van Ginkel FW; Vu HL; Novak MJ; McGhee JR; Mestecky J; Department of Microbiology and The Immunobiology Vaccine Center,; University of Alabama at Birmingham, Birmingham, Alabama; 35294-2170, USA. nghuan@uab.edu

Abstract: Heterosubtypic immunity (HSI) is defined as cross-protection against influenza virus of a different serotype than the virus initially encountered and is thought to be mediated by influenza virus-specific cytotoxic T lymphocytes (CTL). Since gamma interferon (IFN-gamma) stimulates cytotoxic cells, including antigen-specific CTL which may control virus replication by secretion of antiviral cytokines such as tumor necrosis factor alpha and IFN-gamma, we have investigated the mechanism of HSI by analyzing the role of IFN-gamma for HSI in IFN-gamma gene-deleted (IFN-gamma(-/-)) mice. It has been reported that IFN-gamma is not required for recovery from primary infection with influenza virus but is important for HSI. Here, we conclusively show that IFN-gamma is not required for induction of secondary influenza virus-specific CTL responses in mediastinal lymph nodes and HSI to lethal influenza A virus infection. Although T helper 2 (Th2)-type cytokines were upregulated in the lungs of IFN-gamma(-/-) mice after virus challenge, either Th1- or Th2-biased responses could provide heterosubtypic protection. Furthermore, titers of serum-neutralizing and cross-reactive antibodies to conserved nucleoprotein in IFN-gamma(-/-) mice did not differ significantly from those in immunocompetent mice. These results indicate that lack of IFN-gamma does not impair cross-reactive virus-specific immune responses and HSI to lethal infection with influenza virus. Our findings provide new insight for the mechanisms of HSI and should be valuable in the development of protective mucosal vaccines against variant virus strains, such as influenza and human immunodeficiency virus.
Keywords: JOURNAL ARTICLE Adaptation, Physiological Animal Antibodies, Viral/BLOOD/IMMUNOLOGY Cross Reactions Female Gene Deletion IgG/BLOOD/IMMUNOLOGY Immunity, Mucosal/*IMMUNOLOGY Influenza/*IMMUNOLOGY/MORTALITY/VIROLOGY Influenza A Virus/CLASSIFICATION/*IMMUNOLOGY Interferon Type II/DEFICIENCY/GENETICS/*IMMUNOLOGY Interleukins/IMMUNOLOGY Lung/IMMUNOLOGY/VIROLOGY Lymph Nodes/IMMUNOLOGY Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Neutralization Tests Respiratory Mucosa/IMMUNOLOGY/VIROLOGY Spleen/IMMUNOLOGY Support, U.S. Gov't, P.H.S. T-Lymphocytes, Cytotoxic/*IMMUNOLOGY Th1 Cells/IMMUNOLOGY Th2 Cells/IMMUNOLOGY

KWDjournalarticleadaptation,physiologicalanimalantibodies,viral/blood/immunologycrossreactionsfemalegenedeletionigg/blood/immunologyimmunity,mucosal/KWDimmunologyinfluenza/KWDimmunology/mortality/virologyinfluenzaavirus/classification/KWDimmunologyinterferontypeii/deficiency/genetics/KWDimmunologyinterleukins/immunologylung/immunology/virologylymphnodes/immunologymicemice,inbredbalbcmice,inbredc57blmice,knockoutneutralizationtestsrespiratorymucosa/immunology/virologyspleen/immunologysupport,uKWDsKWDgov't,pKWDhKWDsKWDt-lymphocytes,cytotoxic/KWDimmunologyth1cells/immunologyth2cells/immunology
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