title: Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes.
abstract: OBJECTIVE
  It is thought that T cells play a major role in the immune-mediated destruction of beta cells in type 1 diabetes, causing inflammation of the islets of Langerhans (insulitis). The significance of insulitis at the onset of type 1 diabetes is debated, and the role of the T cells poorly understood.
  
  
  METHODS
  In the Diabetes Virus Detection (DiViD) study, pancreatic tissue from six living patients with recent-onset type 1 diabetes was collected. The insulitis was characterised quantitatively by counting CD3(+) T cells, and qualitatively by transcriptome analysis targeting 84 T and B lymphocyte genes of laser-captured microdissected islets. The findings were compared with gene expression in T cells collected from kidney biopsies from allografts with ongoing cellular rejection. Cytokine and chemokine release from isolated islets was characterised and compared with that from islets from non-diabetic organ donors.
  
  
  RESULTS
  All six patients fulfilled the criteria for insulitis (5-58% of the insulin-containing islets in the six patients had ≥ 15 T cells/islet). Of all the islets, 36% contained insulin, with several resembling completely normal islets. The majority (61-83%) of T cells were found as peri-insulitis rather than within the islet parenchyma. The expression pattern of T cell genes was found to be markedly different in islets compared with the rejected kidneys. The islet-infiltrating T cells showed only background levels of cytokine/chemokine release in vitro.
  
  
  CONCLUSIONS
  Insulitis and a significant reserve reservoir for insulin production were present in all six cases of recent-onset type 1 diabetes. Furthermore, the expression patterns and levels of cytokines argue for a different role of the T cells in type 1 diabetes when compared with allograft rejection.
authors.affiliation: Paediatric Department, Oslo University Hospital HF, PO Box 4950, Nydalen, N-0424, Oslo, Norway. lars.krogvold@gmail.com.|Faculty of Medicine, University of Oslo, Oslo, Norway. lars.krogvold@gmail.com.
authors.forename: Lars
authors.initials: L
authors.lastname: Krogvold
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wiberg
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway.|The Intervention Centre, Oslo University Hospital, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Edwin
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Surgery, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Buanes
authors.affiliation: Department of Pathology, Oslo University Hospital, Oslo, Norway.|Centre for Immune Regulation, University of Oslo, Oslo, Norway.
authors.forename: Frode Lars
authors.initials: FL
authors.lastname: Jahnsen
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: Erik
authors.initials: E
authors.lastname: Larsson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Skog
authors.affiliation: Paediatric Department, Oslo University Hospital HF, PO Box 4950, Nydalen, N-0424, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Dahl-Jørgensen
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology* / Q000601:surgery; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D010179:Pancreas / Q000601:surgery*; D013601:T-Lymphocytes / Q000502:physiology*; D055815:Young Adult
chemical_list: D007328:Insulin
keywords: Gene expression; Inflammation; Insulin; Insulitis; Pancreas; T cells; Type 1 diabetes