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Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes.
Babon, Jenny Aurielle B; DeNicola, Megan E; Blodgett, David M; Crèvecoeur, Inne; Buttrick, Thomas S; Maehr, René; Bottino, Rita; Naji, Ali; Kaddis, John; Elyaman, Wassim; James, Eddie A; Haliyur, Rachana; Brissova, Marcela; Overbergh, Lut; Mathieu, Chantal; Delong, Thomas; Haskins, Kathryn; Pugliese, Alberto; Campbell-Thompson, Martha; Mathews, Clayton; Atkinson, Mark A; Powers, Alvin C; Harlan, David M; Kent, Sally C.
Afiliación
  • Babon JA; Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
  • DeNicola ME; Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
  • Blodgett DM; Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
  • Crèvecoeur I; Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
  • Buttrick TS; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Maehr R; Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
  • Bottino R; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania, USA.
  • Naji A; Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
  • Kaddis J; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
  • Elyaman W; Department of Information Sciences, Beckman Research Institute, City of Hope, Duarte, California, USA.
  • James EA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Haliyur R; Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
  • Brissova M; Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Overbergh L; Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Mathieu C; Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
  • Delong T; Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
  • Haskins K; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
  • Pugliese A; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
  • Campbell-Thompson M; Diabetes Research Institute, University of Miami, Miami, Florida, USA.
  • Mathews C; Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.
  • Atkinson MA; Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.
  • Powers AC; Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.
  • Harlan DM; Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Kent SC; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
Nat Med ; 22(12): 1482-1487, 2016 12.
Article en En | MEDLINE | ID: mdl-27798614
A major therapeutic goal for type 1 diabetes (T1D) is to induce autoantigen-specific tolerance of T cells. This could suppress autoimmunity in those at risk for the development of T1D, as well as in those with established disease who receive islet replacement or regeneration therapy. Because functional studies of human autoreactive T cell responses have been limited largely to peripheral blood-derived T cells, it is unclear how representative the peripheral T cell repertoire is of T cells infiltrating the islets. Our knowledge of the insulitic T cell repertoire is derived from histological and immunohistochemical analyses of insulitis, the identification of autoreactive CD8+ T cells in situ, in islets of human leukocyte antigen (HLA)-A2+ donors and isolation and identification of DQ8 and DQ2-DQ8 heterodimer-restricted, proinsulin-reactive CD4+ T cells grown from islets of a single donor with T1D. Here we present an analysis of 50 of a total of 236 CD4+ and CD8+ T cell lines grown from individual handpicked islets or clones directly sorted from handpicked, dispersed islets from nine donors with T1D. Seventeen of these T cell lines and clones reacted to a broad range of studied native islet antigens and to post-translationally modified peptides. These studies demonstrate the existence of a variety of islet-infiltrating, islet-autoantigen reactive T cells in individuals with T1D, and these data have implications for the design of successful immunotherapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoantígenos / Linfocitos T / Antígenos HLA-DQ / Autoinmunidad / Antígeno HLA-A2 / Islotes Pancreáticos / Diabetes Mellitus Tipo 1 Límite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoantígenos / Linfocitos T / Antígenos HLA-DQ / Autoinmunidad / Antígeno HLA-A2 / Islotes Pancreáticos / Diabetes Mellitus Tipo 1 Límite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos