title: Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumour necrosis factor-alpha in patients with recent-onset type 1 diabetes.
abstract: OBJECTIVE
  Type 1A diabetes results from autoimmune destruction of pancreatic beta cells. We examined the involvement of TNF-alpha and IL-1beta, as well as of T cells, macrophages and dendritic cells, in the destruction of beta cells in patients with recent-onset type 1 diabetes.
  
  
  METHODS
  We obtained pancreatic biopsy specimens from six patients with recent-onset type 1 diabetes and analysed these by immunohistochemistry.
  
  
  RESULTS
  T cell infiltration was less common in islets without beta cells (12.5 [0-33.3]%) than in those with beta cells (46.0 [17.4-83.3]%), while macrophages and dendritic cells showed a similar extent of infiltration into islets both with or without beta cells. TNF-alpha was detected in 25.0 (4.3-46.9)% of macrophages and 11.8 (0-40.0)% of dendritic cells infiltrating the islets in samples from each patient, but not at all in T cells. IL-1beta was detected in 1.8 (0-11.3)% of T cells infiltrating the islets with beta cells, while it was found in 19.2 (0-35.3)% of macrophages or 10.7 (0-31.3)% of dendritic cells infiltrating the islets in samples from each patient (all values median [range]).
  
  
  CONCLUSIONS
  Macrophages and dendritic cells infiltrate the islets and produce inflammatory cytokines (TNF-alpha and IL-1beta) during the development of type 1A diabetes.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, and Department of Internal Medicine, Mino City Hospital, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Uno
authors.forename: A
authors.initials: A
authors.lastname: Imagawa
authors.forename: K
authors.initials: K
authors.lastname: Okita
authors.forename: K
authors.initials: K
authors.lastname: Sayama
authors.forename: M
authors.initials: M
authors.lastname: Moriwaki
authors.forename: H
authors.initials: H
authors.lastname: Iwahashi
authors.forename: K
authors.initials: K
authors.lastname: Yamagata
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: T
authors.initials: T
authors.lastname: Hanafusa
authors.forename: J
authors.initials: J
authors.lastname: Miyagawa
authors.forename: I
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D003713:Dendritic Cells / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood
chemical_list: D015703:Antigens, CD; D014409:Tumor Necrosis Factor-alpha