Abstract
Previous studies have shown that vaccine-primed CD4(+) T cells can mediate accelerated clearance of respiratory virus infection. However, the relative contributions of Ab and CD8(+) T cells, and the mechanism of viral clearance, are poorly understood. Here we show that control of a Sendai virus infection by primed CD4(+) T cells is mediated through the production of IFN-gamma and does not depend on Ab. This effect is critically dependent on CD8(+) cells for the expansion of CD4(+) T cells in the lymph nodes and the recruitment of memory CD4(+) T cells to the lungs. Passive transfer of a CD8(+) T cell supernatant into CD8(+) T cell-depleted, hemagglutinin-neuraminidase (HN)(421-436)-immune muMT mice substantially restored the virus-specific memory CD4(+) response and enhanced viral control in the lung. Together, the data demonstrate for the first time that in vivo primed CD4(+) T cells have the capacity to control a respiratory virus infection in the lung by an Ab-independent mechanism, provided that CD8(+) T cell "help" in the form of soluble factor(s) is available during the virus infection. These studies highlight the importance of synergistic interactions between CD4(+) and CD8(+) T cell subsets in the generation of optimal antiviral immunity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Viral / physiology*
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B-Lymphocytes / immunology
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Bronchoalveolar Lavage Fluid / immunology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / virology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / virology
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Cell-Free System / immunology
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Cell-Free System / metabolism
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Epitopes, T-Lymphocyte / immunology
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Female
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HN Protein / immunology*
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Immunization, Passive
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Immunologic Memory*
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Interferon-gamma / physiology
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Lung / immunology
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Lung / virology
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphocyte Depletion
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Male
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Mesentery
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Respirovirus / immunology*
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Respirovirus Infections / genetics
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Respirovirus Infections / immunology
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Respirovirus Infections / prevention & control*
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Respirovirus Infections / virology
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Signal Transduction / immunology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / virology
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T-Lymphocytes, Cytotoxic / immunology
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Viral Load
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Viral Vaccines / administration & dosage
Substances
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Antibodies, Viral
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Epitopes, T-Lymphocyte
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HN Protein
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Peptide Fragments
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Viral Vaccines
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Interferon-gamma