title: Priming of protective T cell responses against virus-induced tumors in mice with human immune system components.
abstract: Many pathogens that cause human disease infect only humans. To identify the mechanisms of immune protection against these pathogens and also to evaluate promising vaccine candidates, a small animal model would be desirable. We demonstrate that primary T cell responses in mice with reconstituted human immune system components control infection with the oncogenic and persistent Epstein-Barr virus (EBV). These cytotoxic and interferon-gamma-producing T cell responses were human leukocyte antigen (HLA) restricted and specific for EBV-derived peptides. In HLA-A2 transgenic animals and similar to human EBV carriers, T cell responses against lytic EBV antigens dominated over recognition of latent EBV antigens. T cell depletion resulted in elevated viral loads and emergence of EBV-associated lymphoproliferative disease. Both loss of CD4(+) and CD8(+) T cells abolished immune control. Therefore, this mouse model recapitulates features of symptomatic primary EBV infection and generates T cell-mediated immune control that resists oncogenic transformation.
authors.affiliation: Laboratory of Viral Immunobiology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.forename: Cagan
authors.initials: C
authors.lastname: Gurer
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Liu
authors.forename: Frida
authors.initials: F
authors.lastname: Arrey
authors.forename: Junji
authors.initials: J
authors.lastname: Sashihara
authors.forename: Gloria
authors.initials: G
authors.lastname: Koo
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007668:Kidney / Q000166:cytology / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D015789:HLA-A2 Antigen