Immunoglobulin A‐deficient mice exhibit altered T helper 1‐type immune responses but retain mucosal immunity to influenza virus

Summary We have previously demonstrated that immunoglobulin A (IgA)−/− knockout (KO) mice exhibit levels of susceptibility to influenza virus infection that are similar to those of their normal IgA+/+ littermates. To understand the mechanism of this apparent mucosal immunity without IgA, immunoglobu...

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Bibliographic Details
Published in:Immunology 2002-03, Vol.105 (3), p.286-294
Main Authors: Zhang, Yongxin, Pacheco, Susan, Acuna, Catherine L., Switzer, Kirsten C., Wang, Ying, Gilmore, Xyanthine, Harriman, Gregory R., Mbawuike, Innocent N.
Format: Article
Language:English
Subjects:
Animals
g-Interferon
Gene Deletion
IgA Deficiency - immunology
Immunity, Mucosal
Immunoglobulin A - genetics
Immunoglobulin A - immunology
Immunoglobulin G - biosynthesis
Influenza Vaccines - immunology
Influenza virus
Interferon-gamma - biosynthesis
Interleukin-4 - biosynthesis
Interleukin-5 - biosynthesis
Mice
Mice, Knockout
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - prevention & control
Th1 Cells - immunology
Vaccination - methods
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Summary:Summary We have previously demonstrated that immunoglobulin A (IgA)−/− knockout (KO) mice exhibit levels of susceptibility to influenza virus infection that are similar to those of their normal IgA+/+ littermates. To understand the mechanism of this apparent mucosal immunity without IgA, immunoglobulin isotype and T helper 1 (Th1)‐type [interferon‐γ (IFN‐γ)] and Th2‐type [interleukin (IL)‐4, IL‐5)] cytokine responses to influenza vaccine were evaluated. Intranasal immunization with influenza virus subunit vaccine plus cholera toxin/cholera toxin B subunit (CT/CTB) induced significant influenza virus‐specific immunoglobulin G (IgG) antibody in the serum and nasal passages of both IgA−/− and IgA+/+ mice, while IgA antibodies were induced only in IgA+/+ mice. IgA KO mice exhibited an IgG1 subclass haemagglutinin (HA)‐specific response but no detectable IgG2a and IgG2b responses. In contrast, IgA+/+ mice exhibited significant IgG1 as well as IgG2a responses. This indicates a predominant Th2‐type response in IgA KO mice compared to normal mice. Following stimulation with influenza virus in vitro, splenic lymphocytes from immunized IgA−/− mice produced significantly lower levels of IFN‐γ than IgA+/+ mice (P 
ISSN:0019-2805
1365-2567
DOI:10.1111/j.1445-5994.2004.00738.x