In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue

Nicole Baumgarth, Anne Kelso

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106 Citations (Scopus)

Abstract

Influenza virus infection induces the local production of gamma interferon (IFN-γ) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN-γ by using monoclonal antibodies. Neutralization of IFN-γ led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum but had little effect on other isotypes. Studies on cells isolated from the lung parenchyma itself revealed that at the height of the immune response the ability of these cells to produce cytokines after antigen or T-cell receptor/CD3 stimulation was not affected. Ex vivo cytolytic activity by lung parenchyma cells, which is induced by infection with this virus in normal mice, was also found to be undisturbed by this treatment, even though anti-IFN-γ antibody activity was recovered from lung lavage samples and sera at all days studied. Surprisingly, in vivo neutralization of IFN-γ led to a significant reduction in the magnitude of the cellular infiltrate in the lung tissue which followed infection, suggesting an involvement of IFN-γ in the mechanisms that regulate increased leucocyte traffic in the inflamed lung parenchyma. This conclusion was supported by findings of differences between mock-treated and anti-IFN-γ-treated mice in the number of CD8+ lung T cells expressing CD49d (α4-integrin) and CD62L at various times after influenza virus infection. This study therefore demonstrates that IFN-γ affects the local cellular response in the respiratory tract as well as the systemic humoral response to influenza virus infection.

Original languageEnglish (US)
Pages (from-to)4411-4418
Number of pages8
JournalJournal of Virology
Volume70
Issue number7
StatePublished - 1996
Externally publishedYes

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interferons
Orthomyxoviridae
interferon-gamma
Cellular Immunity
cell-mediated immunity
Interferons
Interferon-gamma
lungs
Lung
Virus Diseases
neutralization
infection
T-lymphocytes
respiratory system
Respiratory System
mice
cytokines
cells
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue",
abstract = "Influenza virus infection induces the local production of gamma interferon (IFN-γ) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN-γ by using monoclonal antibodies. Neutralization of IFN-γ led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum but had little effect on other isotypes. Studies on cells isolated from the lung parenchyma itself revealed that at the height of the immune response the ability of these cells to produce cytokines after antigen or T-cell receptor/CD3 stimulation was not affected. Ex vivo cytolytic activity by lung parenchyma cells, which is induced by infection with this virus in normal mice, was also found to be undisturbed by this treatment, even though anti-IFN-γ antibody activity was recovered from lung lavage samples and sera at all days studied. Surprisingly, in vivo neutralization of IFN-γ led to a significant reduction in the magnitude of the cellular infiltrate in the lung tissue which followed infection, suggesting an involvement of IFN-γ in the mechanisms that regulate increased leucocyte traffic in the inflamed lung parenchyma. This conclusion was supported by findings of differences between mock-treated and anti-IFN-γ-treated mice in the number of CD8+ lung T cells expressing CD49d (α4-integrin) and CD62L at various times after influenza virus infection. This study therefore demonstrates that IFN-γ affects the local cellular response in the respiratory tract as well as the systemic humoral response to influenza virus infection.",
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T1 - In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue

AU - Baumgarth, Nicole

AU - Kelso, Anne

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N2 - Influenza virus infection induces the local production of gamma interferon (IFN-γ) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN-γ by using monoclonal antibodies. Neutralization of IFN-γ led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum but had little effect on other isotypes. Studies on cells isolated from the lung parenchyma itself revealed that at the height of the immune response the ability of these cells to produce cytokines after antigen or T-cell receptor/CD3 stimulation was not affected. Ex vivo cytolytic activity by lung parenchyma cells, which is induced by infection with this virus in normal mice, was also found to be undisturbed by this treatment, even though anti-IFN-γ antibody activity was recovered from lung lavage samples and sera at all days studied. Surprisingly, in vivo neutralization of IFN-γ led to a significant reduction in the magnitude of the cellular infiltrate in the lung tissue which followed infection, suggesting an involvement of IFN-γ in the mechanisms that regulate increased leucocyte traffic in the inflamed lung parenchyma. This conclusion was supported by findings of differences between mock-treated and anti-IFN-γ-treated mice in the number of CD8+ lung T cells expressing CD49d (α4-integrin) and CD62L at various times after influenza virus infection. This study therefore demonstrates that IFN-γ affects the local cellular response in the respiratory tract as well as the systemic humoral response to influenza virus infection.

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