ArticleFrontiers in immunology2021
Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Renaissance of antiviral CD8Nature reviews. Immunology · 2026Review
- Determinants of Chimeric Antigen Receptor (CAR) T Cell Success: In Vitro and In Vivo Preclinical Assessment.Cancers · 2026Review
- Modeling HIV infection, treatment, rebound, and intervention in human immune organoids.bioRxiv : the preprint server for biology · 2026Article
- Neonatal and pediatric thymic grafts generate similar human T-cell chimerism in humanized mice.Frontiers in immunology · 2026Article
- Humanized Bone Model Identifies BMP6 as a Multifunctional Regulator in Myeloma Bone Disease.Biomolecules · 2025Article
- DUSP11 is an Intracellular Innate Immune Checkpoint in Lung Adenocarcinoma.Cancer immunology research · 2025Article
- Anti-HIV-1 HSPC-based gene therapy with safety kill switch to defend against and attack HIV-1 infection.Molecular therapy. Methods & clinical development · 2025Article
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- Bone marrow stromal cells enhance differentiation of acute myeloid leukemia induced by pyrimidine synthesis inhibitors.American journal of physiology. Cell physiology · 2024Article
- Against all odds: The road to success in the development of human immune reconstitution mice.Animal models and experimental medicine · 2024Review
- Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection.Viruses · 2024Review
- RUNX1 loss renders hematopoietic and leukemic cells dependent on IL-3 and sensitive to JAK inhibition.The Journal of clinical investigation · 2023Article
- A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains.Microorganisms · 2023Article
- The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?Pathogens (Basel, Switzerland) · 2023Review
- Virus-Based Immuno-Oncology Models.Biomedicines · 2022Review
- Learning to Be Elite: Lessons From HIV-1 Controllers and Animal Models on Trained Innate Immunity and Virus Suppression.Frontiers in immunology · 2022Review
- Longitudinal clonal tracking in humanized mice reveals sustained polyclonal repopulation of gene-modified human-HSPC despite vector integration bias.Stem cell research & therapy · 2021Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Humanized bone marrow-liver-thymus (HuBLT) mice are a revolutionary small-animal model that has facilitated the study of human immune function and human-restricted pathogens, including human immunodeficiency virus type 1 (HIV-1). These mice recapitulate many aspects of acute and chronic HIV-1 infection, but exhibit weak and variable T-cell responses when challenged with HIV-1, hindering our ability to confidently detect HIV-1-specific responses or vaccine effects. To identify the cause of this, we comprehensively analyzed T-cell development, diversity, and function in HuBLT mice. We found that virtually all HuBLT were well-reconstituted with T cells and had intact TCRβ sequence diversity, thymic development, and differentiation to memory and effector cells. However, there was poor CD4+ and CD8+ T-cell responsiveness to physiologic stimuli and decreased TH1 polarization that correlated with deficient reconstitution of innate immune cells, in particular monocytes. HIV-1 infection of HuBLT mice showed that mice with higher monocyte reconstitution exhibited greater CD8+ T cells responses and HIV-1 viral evolution within predicted HLA-restricted epitopes. Thus, T-cell responses to immune challenges are blunted in HuBLT mice due to a deficiency of innate immune cells, and future efforts to improve the model for HIV-1 immune response and vaccine studies need to be aimed at restoring innate immune reconstitution.
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