Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice

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 IL2...

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Veröffentlicht in:Immunology 2012-07, Vol.136 (3), p.334-343
Hauptverfasser: Jaiswal, Smita, Pazoles, Pamela, Woda, Marcia, Shultz, Leonard D., Greiner, Dale L., Brehm, Michael A., Mathew, Anuja
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container_end_page 343
container_issue 3
container_start_page 334
container_title Immunology
container_volume 136
creator Jaiswal, Smita
Pazoles, Pamela
Woda, Marcia
Shultz, Leonard D.
Greiner, Dale L.
Brehm, Michael A.
Mathew, Anuja
description 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 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.
doi_str_mv 10.1111/j.1365-2567.2012.03585.x
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subjects Animals
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Antibody Specificity
B-Lymphocytes - immunology
B-Lymphocytes - virology
Base Sequence
dengue
Dengue - immunology
Dengue - prevention & control
Dengue - virology
Dengue fever
Dengue Vaccines - immunology
Dengue Virus - genetics
Dengue Virus - immunology
Fetal Tissue Transplantation
HLA-A2 Antigen - metabolism
human
Humans
Immunity, Humoral
Interferon-gamma - biosynthesis
Liver Transplantation
Medical research
Mice
Mice, Inbred NOD
Mice, SCID
Original
Pathogenesis
RNA, Viral - blood
RNA, Viral - genetics
Stem cells
T cells
T-Lymphocytes - immunology
T-Lymphocytes - virology
Thymus Gland - transplantation
transgenic mice
viral
Viral Load
title Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice
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