ArticleScience translational medicine2012
A model for personalized in vivo analysis of human immune responsiveness.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.Cancer science · 2021Pooled it
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- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance.NPJ breast cancer · 2026Review
- Neonatal and pediatric thymic grafts generate similar human T-cell chimerism in humanized mice.Frontiers in immunology · 2026Article
- Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic.Journal for immunotherapy of cancer · 2025Review
- 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
- Immune Checkpoint Molecules as Biomarkers ofbioRxiv : the preprint server for biology · 2024Article
- Humanized Mouse Models of Bacterial Infections.Antibiotics (Basel, Switzerland) · 2024Review
- Progress, implications, and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement.Animal models and experimental medicine · 2024Review
- Progress in building clinically relevant patient-derived tumor xenograft models for cancer research.Animal models and experimental medicine · 2023Review
- Review
- Humanized mouse models for immuno-oncology research.Nature reviews. Clinical oncology · 2023Review
- Generation of functional human T cell development in NOD/SCID/IL2rγStem cell reports · 2023Article
- Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-derived Xenograft Mouse Model.Journal of visualized experiments : JoVE · 2023Article
- Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue.Frontiers in immunology · 2023Article
- Robust engraftment of fetal nonhuman primate CD34-positive cells in immune-deficient mice.Journal of leukocyte biology · 2022Article
- T1D patient-derived hematopoietic stem cells are programmed to generate Tph, Tfh, and autoimmunity-associated B cell subsets in human immune system mice.Clinical immunology (Orlando, Fla.) · 2022Article
- Defects in Long-Term APC Repopulation Ability of Adult Human Bone Marrow Hematopoietic Stem Cells (HSCs) Compared with Fetal Liver HSCs.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Studies of human immune diseases are generally limited to the analysis of peripheral blood lymphocytes of heterogeneous patient populations. Improved models are needed to allow analysis of fundamental immunologic abnormalities predisposing to disease and in which to assess immunotherapies. Immunodeficient mice receiving human fetal thymus grafts and fetal CD34(+) cells intravenously produce robust human immune systems, allowing analysis of human T cell development and function. However, to use humanized mice to study human immune-mediated disorders, immune systems must be generated from adult hematopoietic cells. Here, we demonstrated robust immune reconstitution in mice with hematopoietic stem cells (HSCs) aspirated from bone marrow of adults with type 1 diabetes (T1D) and healthy control volunteers. In these humanized mice, cryopreservation of human leukocyte antigen allele-matched fetal thymic tissue prevented allogeneic adult HSC rejection. Newly generated T cells, which included regulatory T cells (T(regs)), were functional and self-tolerant and had a diverse repertoire. The immune recognition of these mice mimicked that of the adult CD34(+) cell donor, but the T cell phenotypes were more predominantly "naïve" than those of the adult donors. HSCs from T1D and control donors generated similar numbers of natural T(regs) intrathymically; however, peripheral T cells from T1D subjects showed increased proportions of activated or memory cells compared to controls, suggesting possible HSC-intrinsic differences in T cell homeostasis that might underlie immune pathology in T1D. This "personalized immune" mouse provides a new model for individualized analysis of human immune responses that may provide new insights into not only T1D but also other forms of immune function and dysfunction as well.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.