Title | Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Strowig T, Gurer C, Ploss A, Liu Y-F, Arrey F, Sashihara J, Koo G, Rice CM, Young JW, Chadburn A, Cohen JI, Münz C |
Journal | J Exp Med |
Volume | 206 |
Issue | 6 |
Pagination | 1423-34 |
Date Published | 2009 Jun 08 |
ISSN | 1540-9538 |
Keywords | Animals, Disease Models, Animal, Epstein-Barr Virus Infections, Herpesvirus 4, Human, HLA-A2 Antigen, Humans, Immune System, Kidney, Mice, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Mice, Transgenic, Neoplasms, Spleen, T-Lymphocytes |
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. |
DOI | 10.1084/jem.20081720 |
Alternate Journal | J Exp Med |
PubMed ID | 19487422 |
Grant List | P01CA23766 / CA / NCI NIH HHS / United States / ImNIH / Intramural NIH HHS / United States R01CA101741 / CA / NCI NIH HHS / United States BAA-06-19 / / PHS HHS / United States R01CA083070 / CA / NCI NIH HHS / United States R01CA108609 / CA / NCI NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.