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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
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2013-03-15Keywords
Acute Lung InjuryAnimals
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
Metadata
Show full item recordAbstract
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 siteDOI
10.4049/jimmunol.1201936Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29174PubMed ID
23408839Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.1201936