Analysis of islet inflammation in human type 1 diabetes

A. Wilcox, S.J. Richardson, Adrian Bone, A.K. Foulis, N.G. Morgan

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalClinical and Experimental Immunology
Volume155
Issue number2
DOIs
Publication statusPublished - 2009

Keywords

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

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    Wilcox, A., Richardson, S. J., Bone, A., Foulis, A. K., & Morgan, N. G. (2009). Analysis of islet inflammation in human type 1 diabetes. Clinical and Experimental Immunology, 155(2), 173-181. https://doi.org/10.1111/j.1365-2249.2008.03860.x