Analysis of islet inflammation in human type 1 diabetes.
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.
Willcox
A
A
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Tamar Science Park, Plymouth, UK.
Richardson
S J
SJ
Bone
A J
AJ
Foulis
A K
AK
Morgan
N G
NG
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007328:Insulin / Q000032:analysis; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology; D007515:Islets of Langerhans / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D010195:Pancreatitis / Q000276:immunology* / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D055815:Young Adult
D007328:Insulin