ArticleJournal of virology2009
Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
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Who cites it
191 citing papers in PubMed.
- Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.PLoS pathogens · 2014Trial
- In vivo suppression of HIV by antigen specific T cells derived from engineered hematopoietic stem cells.PLoS pathogens · 2012Trial
- Stepwise Evolution of Immunodeficient Mouse Models: Focus on NCG Strains and Their Applications in Humanized Immune System Research.Vaccines · 2026Review
- Humanized immune system animal models and their recent applications.Animal models and experimental medicine · 2026Review
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Testing the capacity of humanized immune system mice to induce a protective antibody response against the Lyme disease pathogen.Microbiology spectrum · 2026Article
- The application of experimental models for the drug discovery for digestive tumors.Molecular cancer · 2026Review
- NeoThy™ immune-humanized mice can produce anti-drug antibodies to support immunogenicity assessment for biological drug products.Frontiers in immunology · 2026Article
- An HTLV-1-Infected Humanized Mouse Model Expressing HLA-A*02:01 Demonstrates Effective CTL-Mediated Suppression of HTLV-1.Viruses · 2025Article
- Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice.eLife · 2025Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Peripheral human red blood cell development in human immune system mouse model with heme oxygenase-1 deficiency.Blood advances · 2024Article
- Melanoma in people living with HIV: Immune landscape dynamics and the role of immuno- and antiviral therapies.Cancer metastasis reviews · 2024Review
- Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Challenges and innovations in hematopoietic stem cell transplantation: exploring bone marrow niches and new model systems.BMB reports · 2024Review
- Humanized mouse model for vaccine evaluation: an overview.Clinical and experimental vaccine research · 2024Review
- Use of pediatric thymus to humanize mice for HIV-1 mucosal transmission.Scientific reports · 2023Article
- Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection.Microorganisms · 2023Review
- Humanized Mice for Studies of HIV-1 Persistence and Elimination.Pathogens (Basel, Switzerland) · 2023Review
- Gene-edited and -engineered stem cell platform drives immunotherapy for brain metastatic melanomas.Science translational medicine · 2023Article
131 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors.
Funding
Abstract
The generation of humanized BLT mice by the cotransplantation of human fetal thymus and liver tissues and CD34(+) fetal liver cells into nonobese diabetic/severe combined immunodeficiency mice allows for the long-term reconstitution of a functional human immune system, with human T cells, B cells, dendritic cells, and monocytes/macrophages repopulating mouse tissues. Here, we show that humanized BLT mice sustained high-level disseminated human immunodeficiency virus (HIV) infection, resulting in CD4(+) T-cell depletion and generalized immune activation. Following infection, HIV-specific humoral responses were present in all mice by 3 months, and HIV-specific CD4(+) and CD8(+) T-cell responses were detected in the majority of mice tested after 9 weeks of infection. Despite robust HIV-specific responses, however, viral loads remained elevated in infected BLT mice, raising the possibility that these responses are dysfunctional. The increased T-cell expression of the negative costimulator PD-1 recently has been postulated to contribute to T-cell dysfunction in chronic HIV infection. As seen in human infection, both CD4(+) and CD8(+) T cells demonstrated increased PD-1 expression in HIV-infected BLT mice, and PD-1 levels in these cells correlated positively with viral load and inversely with CD4(+) cell levels. The ability of humanized BLT mice to generate both cellular and humoral immune responses to HIV will allow the further investigation of human HIV-specific immune responses in vivo and suggests that these mice are able to provide a platform to assess candidate HIV vaccines and other immunotherapeutic strategies.
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