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Keywords:

  • beta cell;
  • insulitis;
  • T cell;
  • type 1 diabetes

Summary

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.