ArticleClinical and experimental immunology2015
Generation of β cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice.
Article in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- Dual CD8 and TCR editing in regulatory T cells mediates HLA-A2-restricted tissue-specific homing.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Beta cell-targeted PD-1 agonist inhibits cell-mediated autoimmunity in pancreas tissue slices.Science advances · 2026Article
- Type 1 diabetesNPJ autoimmunity · 2026Article
- Immunogenetics and TCR expression patterns together predict future T1D onset from multi-omic datasets.Frontiers in genetics · 2026Article
- Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices.bioRxiv : the preprint server for biology · 2025Article
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
- Modeling cell-mediated immunity in human type 1 diabetes by engineering autoreactive CD8Frontiers in immunology · 2023Article
- Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes.Frontiers in endocrinology · 2022Review
- Review
- Using the T Cell Receptor as a Biomarker in Type 1 Diabetes.Frontiers in immunology · 2021Review
- Next-Generation HLA Sequence Analysis Uncovers Seven HLA-DQ Amino Acid Residues and Six Motifs Resistant to Childhood Type 1 Diabetes.Diabetes · 2020Article
- Immunomodulatory Dual-Sized Microparticle System Conditions Human Antigen Presenting Cells Into a Tolerogenic PhenotypeFrontiers in immunology · 2020Article
- Humanized mouse models of immunological diseases and precision medicine.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Review
- Humanizing the mouse immune system to study splanchnic organ inflammation.The Journal of physiology · 2018Review
- Type 1 Interferons Potentiate Human CD8Diabetes · 2017Article
- T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes.Nature communications · 2017Article
- Type 1 diabetes induction in humanized mice.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics.Cell reports · 2017Article
- Humanized Mouse Models of Clinical Disease.Annual review of pathology · 2017Review
- Avidity and Bystander Suppressive Capacity of Human Regulatory T Cells ExpressingFrontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 5 countries.
Funding
Abstract
Several β cell antigens recognized by T cells in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D) are also T cell targets in the human disease. While numerous antigen-specific therapies prevent diabetes in NOD mice, successful translation of rodent findings to patients has been difficult. A human leucocyte antigen (HLA)-transgenic mouse model incorporating human β cell-specific T cells might provide a better platform for evaluating antigen-specific therapies. The ability to study such T cells is limited by their low frequency in peripheral blood and the difficulty in obtaining islet-infiltrating T cells from patients. We have worked to overcome this limitation by using lentiviral transduction to 'reprogram' primary human CD8 T cells to express three T cell receptors (TCRs) specific for a peptide derived from the β cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP265-273 ) and recognized in the context of the human class I major histocompatibility complex (MHC) molecule HLA-A2. The TCRs bound peptide/MHC multimers with a range of avidities, but all bound with at least 10-fold lower avidity than the anti-viral TCR used for comparison. One exhibited antigenic recognition promiscuity. The β cell-specific human CD8 T cells generated by lentiviral transduction with one of the TCRs released interferon (IFN)-γ in response to antigen and exhibited cytotoxic activity against peptide-pulsed target cells. The cells engrafted in HLA-A2-transgenic NOD-scid IL2rγ(null) mice and could be detected in the blood, spleen and pancreas up to 5 weeks post-transfer, suggesting the utility of this approach for the evaluation of T cell-modulatory therapies for T1D and other T cell-mediated autoimmune diseases.
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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.