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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Babad, J. Mukherjee, G. Follenzi, A. Ali, R. Roep, B. O. Shultz, L. D. Santamaria, P. Yang, O. O. Goldstein, H. Greiner, D. L. DiLorenzo, T. P. |
| Description | Country affiliation: United States Author Affiliation: Babad J ( Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.) |
| Abstract | Several ß 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 ß 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 ß 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 ß 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. |
| File Format | HTM / HTML |
| ISSN | 00099104 |
| e-ISSN | 13652249 |
| DOI | 10.1111/cei.12465 |
| Journal | Clinical & Experimental Immunology |
| Issue Number | 3 |
| Volume Number | 179 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2015-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Immunology Cd8-positive T-lymphocytes Immunology Diabetes Mellitus, Type 1 Genetic Vectors Genetics Immunotherapy, Adoptive Insulin-secreting Cells Lentivirus T-lymphocytes, Cytotoxic Animals Transplantation Cell Survival Glucose-6-phosphatase Hla-a2 Antigen Metabolism Jurkat Cells Mice Mice, Inbred Nod Mice, Knockout Mice, Transgenic Peptide Fragments Receptors, Antigen, T-cell Receptors, Interleukin-2 Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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