Analysis of islet inflammation in human type 1 diabetes

• Published in: Clinical and experimental immunology Vol. 155; no. 2; pp. 173 - 181
• Main Authors: Willcox, A, Richardson, S.J, Bone, A.J, Foulis, A.K, Morgan, N.G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-02-2009; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Adolescent; beta cell; 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-dependent diabetes mellitus; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - pathology; insulitis; 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 cell; T-Lymphocytes, Regulatory - immunology; Translational Studies; type 1 diabetes; Young Adult
• ISSN: 0009-9104; 1365-2249
• 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.