Priming of protective T cell responses against virus-induced tumors in mice with human immune system components.
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.
Strowig
Till
T
Laboratory of Viral Immunobiology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065, USA.
Gurer
Cagan
C
Ploss
Alexander
A
Liu
Yi-Fang
YF
Arrey
Frida
F
Sashihara
Junji
J
Koo
Gloria
G
Rice
Charles M
CM
Young
James W
JW
Chadburn
Amy
A
Cohen
Jeffrey I
JI
Münz
Christian
C
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*
D015789:HLA-A2 Antigen