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    Anti-IFN-gamma and peptide-tolerization therapies inhibit acute lung injury induced by cross-reactive influenza A-specific memory T cells

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    Authors
    Wlodarczyk, Myriam F.
    Kraft, Anke R.
    Chen, Hong D.
    Kenney, Laurie L.
    Selin, Liisa K.
    UMass Chan Affiliations
    Department of Pathology
    Document Type
    Journal Article
    Publication Date
    2013-03-15
    Keywords
    Acute Lung Injury
    Animals
    Antibodies
    CD8-Positive T-Lymphocytes
    Cell Line
    Cricetinae
    Cross Reactions
    Disease Models, Animal
    Epitopes, T-Lymphocyte
    Humans
    *Immune Tolerance
    *Immunologic Memory
    Influenza A virus
    Interferon-gamma
    Lymphocytic Choriomeningitis
    Lymphocytic choriomeningitis virus
    Male
    Mice
    Mice, Inbred C57BL
    Orthomyxoviridae Infections
    Peptide Fragments
    Severity of Illness Index
    Immunology of Infectious Disease
    Respiratory Tract Diseases
    Virus Diseases
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    Link to Full Text
    http://dx.doi.org/10.4049/jimmunol.1201936
    Abstract
    Viral infections have variable outcomes, with severe disease occurring in only few individuals. We hypothesized that this variable outcome could correlate with the nature of responses made to previous microbes. To test this, mice were infected initially with influenza A virus (IAV) and in memory phase challenged with lymphocytic choriomeningitis virus (LCMV), which we show in this study to have relatively minor cross-reactivity with IAV. The outcome in genetically identical mice varied from mild pneumonitis to severe acute lung injury with extensive pneumonia and bronchiolization, similar to that observed in patients who died of the 1918 H1N1 pandemic. Lesion expression did not correlate with virus titers. Instead, disease severity directly correlated with and was predicted by the frequency of IAV-PB1703- and IAV-PA224-specific responses, which cross-reacted with LCMV-GP34 and LCMV-GP276, respectively. Eradication or functional ablation of these pathogenic memory T cell populations, using mutant-viral strains, peptide-based tolerization strategies, or short-term anti-IFN-gamma treatment, inhibited severe lesions such as bronchiolization from occurring. Heterologous immunity can shape outcome of infections and likely individual responses to vaccination, and can be manipulated to treat or prevent severe pathology.
    Source
    J Immunol. 2013 Mar 15;190(6):2736-46. doi: 10.4049/jimmunol.1201936. Link to article on publisher's site
    DOI
    10.4049/jimmunol.1201936
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/29174
    PubMed ID
    23408839
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.1201936
    Scopus Count
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