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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\u2013 and IAV-PA224\u2013specific 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\u2013IFN-\u03b3 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1201936","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T04:36:51Z","timestamp":1360816611000},"page":"2736-2746","source":"Crossref","is-referenced-by-count":34,"title":["Anti\u2013IFN-\u03b3 and Peptide-Tolerization Therapies Inhibit Acute Lung Injury Induced by Cross-Reactive Influenza A\u2013Specific Memory T Cells"],"prefix":"10.1093","volume":"190","author":[{"given":"Myriam F","family":"Wlodarczyk","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and Program in Immunology and Virology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke R","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and Program in Immunology and Virology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong D","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and Program in Immunology and Virology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie L","family":"Kenney","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and Program in Immunology and Virology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liisa K","family":"Selin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and Program in Immunology and Virology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,3,15]]},"reference":[{"key":"2025032406405841700_r1","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nri2802","article-title":"Immunity and immunopathology to viruses: what decides the outcome?","volume":"10","author":"Rouse","year":"2010","journal-title":"Nat. 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