Analysis of islet inflammation in human type 1 diabetes

Clinical and Experimental Immunology - Tập 155 Số 2 - Trang 173-181 - 2009
Abby O’Connell1, Sarah J. Richardson1, Adrian J. Bone2, Alan K. Foulis3, Noel G. Morgan1
1Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Tamar Science Park, Plymouth,
2School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulescoomb, Brighton, and
3Department of Pathology, Royal Infirmary, Glasgow,UK

Tóm tắt

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.

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Thông tin xuất bản

Clinical and Experimental Immunology

Tập 155 Số 2

173-181

Thông tin tác giả