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Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice
Author(s) -
Jaiswal Smita,
Pazoles Pamela,
Woda Marcia,
Shultz Leonard D.,
Greiner Dale L.,
Brehm Michael A.,
Mathew Anuja
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2012.03585.x
Subject(s) - biology , humanized mouse , virology , immunology , immune system , haematopoiesis , dengue fever , dengue virus , antibody , stem cell , genetics
Summary 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 IL2rγ 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‐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.