Analysis of islet inflammation in human type 1 diabetes

Wilcox, A., Richardson, S.J., Bone, Adrian, Foulis, A.K. and Morgan, N.G. (2009) Analysis of islet inflammation in human type 1 diabetes Clinical and Experimental Immunology, 155 (2). pp. 173-181. ISSN 0009-9104

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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.

Item Type: Journal article
Uncontrolled Keywords: beta cell; insulitis; T cell; type 1 diabetes
Subjects: C000 Biological and Biomedical Sciences
DOI (a stable link to the resource): 10.1111/j.1365-2249.2008.03860.x
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
Depositing User: Sarah Flux
Date Deposited: 31 Aug 2010 10:02
Last Modified: 13 Mar 2015 12:08

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