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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 \u03b2 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 \u2018reprogram\u2019 primary human CD8 T cells to express three T cell receptors (TCRs) specific for a peptide derived from the \u03b2 cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP265\u2013273) 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 \u03b2 cell-specific human CD8 T cells generated by lentiviral transduction with one of the TCRs released interferon (IFN)-\u03b3 in response to antigen and exhibited cytotoxic activity against peptide-pulsed target cells. The cells engrafted in HLA-A2-transgenic NOD-scid IL2r\u03b3null 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.<\/jats:p>","DOI":"10.1111\/cei.12465","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T03:07:16Z","timestamp":1412910436000},"page":"398-413","source":"Crossref","is-referenced-by-count":28,"title":["Generation of \u03b2 cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice"],"prefix":"10.1093","volume":"179","author":[{"given":"J","family":"Babad","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Follenzi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Piemonte Orientale \u2018A. Avogadro\u2019, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B O","family":"Roep","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L D","family":"Shultz","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Santamaria","sequence":"additional","affiliation":[{"name":"Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Canada"},{"name":"Department of Microbiology, Immunology, and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Canada"},{"name":"Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O O","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Geffen School of Medicine, University of California, Los Angeles, CA, USA"},{"name":"Department of Microbiology, Immunology, and Molecular Genetics, Geffen School of Medicine, University of California, Los Angeles, CA, USA"},{"name":"AIDS Healthcare Foundation, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA"},{"name":"Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D L","family":"Greiner","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T P","family":"DiLorenzo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA"},{"name":"Department of Medicine (Division of Endocrinology), Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,16]]},"reference":[{"key":"2021122010103902800_cei12465-bib-0001","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00281-010-0204-1","article-title":"Mouse models for the study of autoimmune type 1 diabetes: a NOD to similarities and differences to human disease","volume":"33","author":"Driver","year":"2011","journal-title":"Semin 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