Diabetes and other autoimmune endocrine diseases

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

Thursday, June 15
5:45 PM - 7:00 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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                        Eddie James

                        Assistant Member
                        Benaroya Research Institute

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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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