title: Memory T cells generated by prior exposure to influenza cross react with the novel H7N9 influenza virus and confer protective heterosubtypic immunity.
abstract: Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Sean R
authors: SR
authors: McMaster
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Jon D
authors: JD
authors: Gabbard
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Dimitris G
authors: DG
authors: Koutsonanos
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Richard W
authors: RW
authors: Compans
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Ralph A
authors: RA
authors: Tripp
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: S Mark
authors: SM
authors: Tompkins
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Jacob E
authors: JE
authors: Kohlmeier
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines