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Cytometric analysis revealed enrichment of T stem cell memory\u2013like (TSCM-like) cells (CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD45RA\n                    <jats:sup>+<\/jats:sup>\n                    CD27\n                    <jats:sup>+<\/jats:sup>\n                    CD28\n                    <jats:sup>+<\/jats:sup>\n                    CCR7\n                    <jats:sup>+<\/jats:sup>\n                    CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    ) in T1D pLNs. scRNA-seq indicated an elevated inflammatory cytokine gene signature (\n                    <jats:italic>IFITM3<\/jats:italic>\n                    ,\n                    <jats:italic>LTB<\/jats:italic>\n                    ) along with regulators of terminal differentiation (\n                    <jats:italic>BCL6<\/jats:italic>\n                    ,\n                    <jats:italic>BCL3<\/jats:italic>\n                    ), coupled with downregulation of exhaustion-associated genes (\n                    <jats:italic>DUSP2<\/jats:italic>\n                    ,\n                    <jats:italic>NR4A2<\/jats:italic>\n                    ,\n                    <jats:italic>TSC22D3<\/jats:italic>\n                    ) in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in T1D pLNs. Immune response enrichment analysis (IREA) indicated IL-15 signaling as a significant driver of these phenotypes. Integrated TCR and transcriptomics analysis revealed a cluster of diverse naive-like CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell clones in T1D pLNs. Comparison of pLNs and pancreatic tissue slice isolates indicated sharing of effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, with enhanced terminal effector signatures within the pancreas relative to paired pLNs. Multiplex imaging revealed differential localization of T cell factor 1 (TCF1)- and thymocyte selection-associated high mobility group box protein (TOX)-expressing T cells in the pancreas, with islet-proximal TCF1\n                    <jats:sup>+<\/jats:sup>\n                    TOX\n                    <jats:sup>+<\/jats:sup>\n                    cells displaying a mixture of activation and exhaustion-associated phenotypes. Thus, we provide multimodal cellular profiles enriched in T1D tissues for consideration in therapeutic targeting.\n                  <\/jats:p>","DOI":"10.1172\/jci196445","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:01:18Z","timestamp":1789408878000},"source":"Crossref","is-referenced-by-count":1,"title":["Immune dysregulation and stem-like CD8+ T cell enrichment in type 1 diabetes pancreatic lymph nodes"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7878-0014","authenticated-orcid":true,"given":"Leeana D.","family":"Peters","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard R.","family":"Seay","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Posgai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed L.","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive H.","family":"Wasserfall","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"},{"name":"Department of Pediatrics, College of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-476X","authenticated-orcid":true,"given":"Rhonda","family":"Bacher","sequence":"additional","affiliation":[{"name":"Diabetes Institute,"},{"name":"Department of Biostatistics, College of Public Health and Health Professions, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4331-2202","authenticated-orcid":true,"given":"Maigan A.","family":"Brusko","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Brusko","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine,"},{"name":"Diabetes Institute,"},{"name":"Department of Pediatrics, College of Medicine,"},{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3245"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0341-6"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030966"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2016.04.013"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04248-x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0091"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0090"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1168"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003099"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07172-1"},{"issue":"9","key":"B11","doi-asserted-by":"crossref","DOI":"10.2337\/db15-er09a","article-title":"Erratum. 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