Diabetes and other autoimmune endocrine diseases

Broad Repertoire of Autoreactive T Cells from the Islets of Donors with Type 1 Diabetes

Thursday, June 15
4:18 PM - 4:31 PM

By necessity, most of our knowledge concerning islet-autoreactive T cells comes from the peripheral blood of individuals with type 1 diabetes (T1D). A significant knowledge gap exists in our understanding of the repertoire of islet-infiltrating, islet-autoreactive T cells.From isolated, handpicked islets from pancreata of 12 donors (5 month-20 year disease duration) with T1D,we isolated, by direct growth from islets or by FACS-sorting of T cells from enzyme-dispersed islets, 300 T cell clones/lines, 5 T cell lines from 1/7 donors without T1D, and no lines from 2 donors with type 2 diabetes. To date, in this ongoing project, from 50 islet-derived T cell lines or clones have been examined and nineteen CD4+ T cell lines/clones were found to be reactive with a broad range of islet-derived peptides. Thirteen lines/clones reactive were reactive with known peptide targets and 6 lines/clones were reactive with post-translationally modified islet peptides. All autoreactive T cell lines secreted pro-inflammatory cytokines. The remaining T cell lines/clones await determination of reactivity: this includes 30 CD8+ T cell lines and the separation and purification of 102 T cell lines which grew from islets of as mixtures of CD4+ and CD8+ T cells. These studies are a major step forward in defining the repertoire of islet infiltrating, autoreactive T cells. These reactivities should impact the design of the induction of autoantigen-specific therapeutic efforts attempting to benefit subjects at-risk for, with recently diagnosed, and with established T1D in combination with islet replacement or regeneration.

Sally Kent

University of Massachusetts Medical Center

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Jenny Aurielle Babon

University of Massachusetts Medical School

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Megan DeNIcola

University of Massachusetts Medical School

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David Blodgett

University of Massachusetts Medical School

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Inne Crèvecoeur

KU Leuven

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Thomas Buttrick

Brigham and Women’s Hospital and Harvard Medical School

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René Maehr

University of Massachusetts Medical School

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Rita Bottino

Allegheny-Singer Research Institute

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Ali Naji

University of Pennsylvania School of Medicine

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John Kaddis

Beckman Research Institute, City of Hope

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Wassim Elyaman

Brigham and Women’s Hospital and Harvard Medical School

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Rachana Haliyur

Vanderbilt University

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Marcela Brissova

Vanderbilt University

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Lut Overbergh

KU Leuven

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Chantal Mathieu

KU Leuven

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Thomas Delong

University of Colorado

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Katie Haskins

University of Colorado

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Alberto Pugliese

University of Miami, Miami

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Martha Campbell-Thompson

University of Florida

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Clayton Mathews

University of Florida

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Mark Atkinson

University of Florida

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Alvin Powers

Vanderbilt University, Vanderbilt University Medical Center, and VA Tennessee Valley Healthcare System

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David Harlan

University of Massachusetts Medical School

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Broad Repertoire of Autoreactive T Cells from the Islets of Donors with Type 1 Diabetes



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