ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Humanized mice as a model for aberrant responses in human T cell immunotherapy.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.Frontiers in medicine · 2020Pooled it
- Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis.BMC medicine · 2015Pooled it
- Nephrotoxicity of Immune Checkpoint Inhibitors in Mice with a Human Immune System.bioRxiv : the preprint server for biology · 2026Article
- The Sunrise of Tertiary Lymphoid Structures in Cancer.Immunological reviews · 2025Review
- Pathological findings of immunotherapy-induced nephrotoxicity in a humanized immune system mouse model.Kidney international · 2025Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Characterization of double humanized BLT-mice with stable engraftment of a human gut bacterial microbiome.Frontiers in microbiomes · 2024Article
- Emerging strategies for engineering Escherichia coli Nissle 1917-based therapeutics.Trends in pharmacological sciences · 2022Review
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- Humanized Mouse Models for the Study of Periodontitis: An Opportunity to Elucidate Unresolved Aspects of Its Immunopathogenesis and Analyze New Immunotherapeutic Strategies.Frontiers in immunology · 2021Review
- Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes.Frontiers in immunology · 2021Article
- Humanized mouse models of genetic immune disorders and hematological malignancies.Biochemical pharmacology · 2020Review
- The development of human immune system mice and their use to study tolerance and autoimmunity.Journal of translational autoimmunity · 2019Review
- A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System.Journal of visualized experiments : JoVE · 2019Article
- Intratumoral delivery of antigen with complement C3-bound liposomes reduces tumor growth in mice.Nanomedicine : nanotechnology, biology, and medicine · 2019Article
- Humanized Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Cell-Based Therapies.Frontiers in immunology · 2019Review
- Microbiota control immune regulation in humanized mice.JCI insight · 2017Article
- Human immune system mouse models of Ebola virus infection.Current opinion in virology · 2017Review
- Modeling of Patient-Derived Xenografts in Colorectal Cancer.Molecular cancer therapeutics · 2017Article
- Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis.Molecular therapy oncolytics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Immune-deficient mice, reconstituted with human stem cells, have been used to analyze human immune responses in vivo. Although they have been used to study immune responses to xenografts, allografts, and pathogens, there have not been models of autoimmune disease in which the mechanisms of the pathologic process can be analyzed. We have found that reconstituted "humanized" mice treated with anti-CTLA-4 Ab (ipilimumab) develop autoimmune disease characterized by hepatitis, adrenalitis, sialitis, anti-nuclear Abs, and weight loss. Induction of autoimmunity involved activation of T cells and cytokine production, and increased infiltration of APCs. When anti-CTLA-4 mAb-treated mice were cotreated with anti-CD3 mAb (teplizumab), hepatitis and anti-nuclear Abs were no longer seen and weight loss did not occur. The anti-CD3 blocked proliferation and activation of T cells, release of IFN-γ and TNF, macrophage infiltration, and release of IP-10 that was induced with anti-CTLA-4 mAb. We also found increased levels of T regulatory cells (CD25(+)CD127(-)) in the spleen and mesenteric lymph nodes in the mice treated with both Abs and greater constitutive phosphorylation of STAT5 in T regulatory cells in spleen cells compared with mice treated with anti-CTLA-4 mAb alone. We describe a model of human autoimmune disease in vivo. Humanized mice may be useful for understanding the mechanisms of biologics that are used in patients. Hepatitis, lymphadenopathy, and other inflammatory sequelae are adverse effects of ipilimumab treatment in humans, and this study may provide insights into this pathogenesis and the effects of immunologics on autoimmunity.
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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.