Sally C Kent1, Stuart I Mannering2,3, Aaron W Michels4, Jenny Aurielle B Babon5. 1. Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, ASC7-2041, University of Massachusetts Medical School, Worcester, MA, 01605, USA. Sally.Kent@umassmed.edu. 2. Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria, 3065, Australia. 3. Department of Medicine, University of Melbourne, St. Vincent's Hospital, Fitzroy, Victoria, 3065, Australia. 4. Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. 5. Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, ASC7-2041, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Abstract
PURPOSE OF REVIEW: Autoimmune-mediated destruction of insulin-producing β-cells within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable. Previously, our understanding of the β-cell specific T cell repertoire was based on studies of autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D; more recently, investigations have included immunohistochemical analysis of some T cell specificities in the pancreas from organ donors with T1D. Now, we are able to examine live, islet-infiltrating T cells from donors with T1D. RECENT FINDINGS: Analysis of the T cell repertoire isolated directly from the pancreatic islets of donors with T1D revealed pro-inflammatory T cells with targets of known autoantigens, including proinsulin and glutamic acid decarboxylase, as well as modified autoantigens. We have assayed the islet-infiltrating T cell repertoire for autoreactivity and function directly from the inflamed islets of T1D organ donors. Design of durable treatments for prevention of or therapy for T1D requires understanding this repertoire.
PURPOSE OF REVIEW: Autoimmune-mediated destruction of insulin-producing β-cells within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable. Previously, our understanding of the β-cell specific T cell repertoire was based on studies of autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D; more recently, investigations have included immunohistochemical analysis of some T cell specificities in the pancreas from organ donors with T1D. Now, we are able to examine live, islet-infiltrating T cells from donors with T1D. RECENT FINDINGS: Analysis of the T cell repertoire isolated directly from the pancreatic islets of donors with T1D revealed pro-inflammatory T cells with targets of known autoantigens, including proinsulin and glutamic acid decarboxylase, as well as modified autoantigens. We have assayed the islet-infiltrating T cell repertoire for autoreactivity and function directly from the inflamed islets of T1D organ donors. Design of durable treatments for prevention of or therapy for T1D requires understanding this repertoire.
Entities:
Keywords:
Autoreactivity; Human; Islets of Langerhans; T cell
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