Analysis of islet inflammation in human type 1 diabetes

Clin Exp Immunol. 2009 Feb;155(2):173-81. doi: 10.1111/j.1365-2249.2008.03860.x.


The immunopathology of type 1 diabetes (T1D) has proved difficult to study in man because of the limited availability of appropriate samples, but we now report a detailed study charting the evolution of insulitis in human T1D. Pancreas samples removed post-mortem from 29 patients (mean age 11.7 years) with recent-onset T1D were analysed by immunohistochemistry. The cell types constituting the inflammatory infiltrate within islets (insulitis) were determined in parallel with islet insulin content. CD8(+) cytotoxic T cells were the most abundant population during insulitis. Macrophages (CD68(+)) were also present during both early and later insulitis, although in fewer numbers. CD20(+) cells were present in only small numbers in early insulitis but were recruited to islets as beta cell death progressed. CD138(+) plasma cells were infrequent at all stages of insulitis. CD4(+) cells were present in the islet infiltrate in all patients but were less abundant than CD8(+) or CD68(+) cells. Forkhead box protein P3(+) regulatory T cells were detected in the islets of only a single patient. Natural killer cells were detected rarely, even in heavily inflamed islets. The results suggest a defined sequence of immune cell recruitment in human T1D. They imply that both CD8(+) cytotoxic cells and macrophages may contribute to beta cell death during early insulitis. CD20(+) cells are recruited in greatest numbers during late insulitis, suggesting an increasing role for these cells as insulitis develops. Natural killer cells and forkhead box protein P3(+) T cells do not appear to be required for beta cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Insulin / analysis
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / pathology
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology
  • Killer Cells, Natural / immunology
  • Male
  • Pancreatitis / immunology*
  • Pancreatitis / pathology
  • Plasma Cells / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Young Adult


  • Insulin