Journal
IMMUNOLOGY
Volume 136, Issue 3, Pages 334-343Publisher
WILEY
DOI: 10.1111/j.1365-2567.2012.03585.x
Keywords
dengue; human; T cells; transgenic mice; viral
Categories
Funding
- National Institute of Allergy and Infectious Diseases [U19 AI57319, U19 AI057234]
- Juvenile Diabetes Research Foundation
- Helmsley Foundation
- National Institutes of Health (NIH) [CA34196]
- NIH Diabetes Endocrinology Research Center (DERC) [DK52530]
- USAMRID
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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 IL2r?null 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-? 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.
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