Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice
Article first published online: 1 JUN 2012
© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd
Volume 136, Issue 3, pages 334–343, July 2012
How to Cite
Jaiswal, S., Pazoles, P., Woda, M., Shultz, L. D., Greiner, D. L., Brehm, M. A. and Mathew, A. (2012), Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice. Immunology, 136: 334–343. doi: 10.1111/j.1365-2567.2012.03585.x
- Issue published online: 1 JUN 2012
- Article first published online: 1 JUN 2012
- Accepted manuscript online: 2 MAR 2012 01:41PM EST
- Received 03 January 2012; revised 21 February 2012; accepted 24 February 212.
- T cells;
- transgenic mice;
Dengue is a mosquito-borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD-scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co-transplantation of human fetal thymus and liver tissues into NSG (BLT-NSG) mice. Enhanced DENV-specific antibody titres were found in the sera of BLT-NSG mice compared with human cord blood haematopoietic stem cell-engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT-NSG mice secreted DENV-specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT-NSG mice secreted interferon-γ in response to overlapping DENV peptide pools and HLA-A2 restricted peptides. The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections.