Analysis of islet inflammation in human type 1 diabetes
Open accessAbstract
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 insuliti…
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FOXP3+ cells (regulatory T cells) and natural killer cells are rare in the insulitis lesion.
“Surprisingly, FOXP3+ cells (ie, regulatory T cells; a population of intense research interest2) and natural killer cells are rare in this lesion.”
From Type 1 diabetes (2014) · cites this paper as [62]
Although it is often stated that symptoms occur when 90-95% of β cells are lost, diagnosis of type 1 diabetes can occur when roughly two-thirds of the islets are devoid of insulin-producing cells.
“Although it is often stated that symptoms occur when 90–95% of β cells are lost, diagnosis of type 1 diabetes can occur when roughly two-thirds of the islets are devoid of insulin-producing cells.61,62”
From Type 1 diabetes (2014) · cites this paper as [62]
CD8+ T cells are the most predominant population within the insulitis lesion, followed by macrophages (CD68+), CD4+ T cells, B lymphocytes (CD20+), and plasma cells (CD138+).
“In terms of potential pathogenic mechanisms, CD8+ T cells are the most predominant population within the insulitis lesion, followed by (in declining order) macrophages (CD68+), CD4+ T cells, B lymphocytes (CD20+), and plasma cells (CD138+).62”
From Type 1 diabetes (2014) · cites this paper as [62]
Among individuals who have had type 1 diabetes for more than 5 years, most of the remaining islets are insulin deficient, containing a normal complement of other hormone secreting cells.
“Among individuals who have had type 1 diabetes for more than 5 years, most of the remaining islets are insulin deficient, containing a normal complement of other hormone secreting cells (ie, α cells that secrete glucagon, δ cells that secrete somatostatin, and PP cells that secrete pancreatic polypeptide).62”
From Type 1 diabetes (2014) · cites this paper as [62]
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- Authors
- Willcox, A., Richardson, S. J., Bone, A. J., Foulis, A. K., & Morgan, N. G.
- Affiliations
- University of Plymouth (GB)
- University of Brighton (GB)
- Glasgow Royal Infirmary (GB)
- Corresponding author
- Morgan, N G
- Venue
- Clinical and Experimental Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-12-11
- Volume
- 155
- Issue
- 2
- Pages
- 173-181
- ISSN
- 0009-9104 (ISSN-L)
- 1365-2249
- PMC
- PMC2675247
- OpenAlex
- W2050995545
- Cited by
- 712
- References
- 1
- Citations by year
- 2026: 19 · 2025: 32 · 2024: 41 · 2023: 44 · 2022: 37 · 2021: 50 · 2020: 39 · 2019: 45 · 2018: 44 · 2017: 47 · 2016: 42 · 2015: 49 · 2014: 53 · 2013: 33 · 2012: 41
- FWCI
- 18.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical & Experimental Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion)
- Funders
- Diabetes UK
- European Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- type 1 diabetes, insulitis, beta-cell death, CD8+ cytotoxic T lymphocytes, macrophages, CD20+ B cells, CD4+ T cells, regulatory T cells, natural killer cells, plasma cells, immune cell recruitment, immunopathology
- MeSH terms
- Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Humans, Infant, Insulin, Islets of Langerhans, Killer Cells, Natural, Male, Pancreatitis, Plasma Cells, Disease Progression, T-Lymphocytes, Regulatory, Insulin-Secreting Cells, Young Adult
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