title: Demonstration of Tissue Resident Memory CD8 T Cells in Insulitic Lesions in Adult Patients with Recent-Onset Type 1 Diabetes.
abstract: Subtypes of CD8+T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3+T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8+T cells in the insulitic lesions to display a tissue resident memory T cell (TRM) (CD8+CD69+CD103+) phenotype in T1D subjects. Most TRMcells were located in the insulitic lesion in the endocrine-exocrine interface. TRMcells were also sporadically found in islets of control subjects. Moreover, gene expression analysis showed a lack of active transcription of genes associated with acute inflammatory or cytotoxic T-cell responses. We present evidence that a substantial proportion of T cells in insulitic lesions of recent-onset T1D patients are TRMcells and not classic cytotoxic CD8+T cells. Our findings highlight the need for further analysis of the T cells involved in insulitis to elucidate their role in the etiology of T1D.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Electronic address: enida.kuric@igp.uu.se.
authors.forename: Enida
authors.initials: E
authors.lastname: Kuric
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Seiron
authors.affiliation: Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Krogvold
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Surgery, The Intervention Centre, Oslo University Hospital, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Edwin
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Buanes
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Endocrinology, Oslo University Hospital, Oslo, Norway.
authors.forename: Kristian F
authors.initials: KF
authors.lastname: Hanssen
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Skog
authors.affiliation: Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Dahl-Jørgensen
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
mesh_terms: D000328:Adult; D015551:Autoimmunity / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007328:Insulin / Q000378:metabolism*; D008297:Male
chemical_list: D007328:Insulin