Viral infections induce CD8 T cell expansion and interferon (IFN)-γ production for defense, but the innate cytokines shaping these responses have not been identified. Although interleukin (IL)-12 has the potential to contribute, IL-12–dependent T cell IFN-γ has not been detected during viral infections. Moreover, certain viruses fail to induce IL-12, and elicit high levels of IFN-α/β to negatively regulate it. The endogenous factors promoting virus-induced T cell IFN-γ production were defined in studies evaluating CD8 T cell responses during lymphocytic choriomeningitis virus infections of mice. Two divergent supporting pathways were characterized. Under normal conditions of infections, the CD8 T cell IFN-γ response was dependent on endogenous IFN-α/β effects, but was IL-12 independent. In contrast, in the absence of IFN-α/β functions, an IL-12 response was revealed and substituted an alternative pathway to IFN-γ. IFN-α/β–mediated effects resulted in enhanced, but the alternative pathway also promoted, resistance to infection. These observations define uniquely important IFN-α/β–controlled pathways shaping T cell responses during viral infections, and demonstrate plasticity of immune responses in accessing divergent innate mechanisms to achieve similar ultimate goals.
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19 April 1999
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April 19 1999
Two Roads Diverged: Interferon α/β– and Interleukin 12–mediated Pathways in Promoting T Cell Interferon γ Responses during Viral Infection
Leslie P. Cousens,
Leslie P. Cousens
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
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Ron Peterson,
Ron Peterson
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
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Sang Hsu,
Sang Hsu
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
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Andrew Dorner,
Andrew Dorner
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
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John D. Altman,
John D. Altman
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
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Rafi Ahmed,
Rafi Ahmed
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
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Christine A. Biron
Christine A. Biron
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
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Leslie P. Cousens
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
Ron Peterson
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
Sang Hsu
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
Andrew Dorner
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
John D. Altman
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
Rafi Ahmed
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
Christine A. Biron
From the *Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the ‡Genetics Institute, Inc., Andover, Massachusetts 01810; and the §Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
Address correspondence to Christine A. Biron, Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Box G-B629, Brown University, Providence, RI 02912. Phone: 401-863-2921; Fax: 401-863-9045; E-mail: [email protected]
Received:
December 29 1998
Revision Received:
February 22 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (8): 1315–1328.
Article history
Received:
December 29 1998
Revision Received:
February 22 1999
Citation
Leslie P. Cousens, Ron Peterson, Sang Hsu, Andrew Dorner, John D. Altman, Rafi Ahmed, Christine A. Biron; Two Roads Diverged: Interferon α/β– and Interleukin 12–mediated Pathways in Promoting T Cell Interferon γ Responses during Viral Infection . J Exp Med 19 April 1999; 189 (8): 1315–1328. doi: https://doi.org/10.1084/jem.189.8.1315
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