Priming of protective T cell responses against virus-induced tumors in mice with human immune system components

Till Strowig, Cagan Gurer, Alexander Ploss, Yi Fang Liu, Frida Arrey, Junji Sashihara, Gloria Koo, Charles M. Rice, James W. Young, Amy Chadburn, Jeffrey I. Cohen, Christian Münz

Research output: Contribution to journalArticle

195 Scopus citations

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-γ-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.

Original languageEnglish (US)
Pages (from-to)1423-1434
Number of pages12
JournalJournal of Experimental Medicine
Volume206
Issue number6
DOIs
StatePublished - Jun 8 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Strowig, T., Gurer, C., Ploss, A., Liu, Y. F., Arrey, F., Sashihara, J., Koo, G., Rice, C. M., Young, J. W., Chadburn, A., Cohen, J. I., & Münz, C. (2009). Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. Journal of Experimental Medicine, 206(6), 1423-1434. https://doi.org/10.1084/jem.20081720