{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:38:27Z","timestamp":1790048307837,"version":"4.0.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Identifying \u03b2 cell autoantigen-reactive T cells that are involved in the pathogenesis of type 1 diabetes has been troublesome for many laboratories. Disease-relevant autoreactive T cells should be in vivo Ag experienced. The aim of this study was to test this hypothesis and then use this principle as a strategy for identifying diabetes-relevant autoreactive T cells. In this study, a CSFE dilution assay was used to detect glutamic acid decarboxylase 65 (GAD65)- and insulin-responsive T cells and HLA-0201*-GAD65114\u2013122 pentamers were used to detect CD8+ GAD-responsive T cells in memory CD45RO+ and naive CD45RO\u2212 cell populations from patients with type 1 diabetes and healthy control subjects. T cell proliferative history was evaluated by flow cytometry telomere length measurement. CD4+ and CD8+ T cells specific for GAD65 and insulin were present in patients with type 1 diabetes and control subjects. Within the naive CD45RO\u2212 cells, CD4+ and CD8+ T cell responses were similar between patients and controls. Within the memory CD45RO+ cells, CD4+ T cell responses against whole GAD65 and insulin and HLA-0201*-GAD65114\u2013122 pentamer-positive CD8+ T cells were found in patients with type 1 diabetes, but not in control subjects (p &amp;lt; 0.05 for all). Responding cells from the CD45RO+ T cell population had substantially shorter telomere lengths than responding cells from the CD45RO\u2212 cell population. Diabetes-specific autoreactive T cells in the circulation have uniquely undergone sustained in vivo proliferation and differentiation into memory T cells. Prior selection of these cells is possible and is a way to identify diabetes-relevant target Ags and epitopes.<\/jats:p>","DOI":"10.4049\/jimmunol.179.9.5785","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:27:18Z","timestamp":1397849238000},"page":"5785-5792","source":"Crossref","is-referenced-by-count":107,"title":["Evidence for In Vivo Primed and Expanded Autoreactive T Cells as a Specific Feature of Patients with Type 1 Diabetes"],"prefix":"10.1093","volume":"179","author":[{"given":"Paolo","family":"Monti","sequence":"first","affiliation":[{"name":"Telethon-Juvenile Diabetes Research Foundation Center for Beta Cell Replacement, San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Scirpoli","sequence":"additional","affiliation":[{"name":"Telethon-Juvenile Diabetes Research Foundation Center for Beta Cell Replacement, San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Rigamonti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya","family":"Mayr","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Jaeger","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bonfanti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Chiumello","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette G","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezio","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Telethon-Juvenile Diabetes Research Foundation Center for Beta Cell Replacement, San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,11,1]]},"reference":[{"key":"2026012809320902000_R1","first-page":"221","volume-title":"Lancet","year":"2001"},{"key":"2026012809320902000_R2","first-page":"232","volume-title":"Immunol. 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