Journal
DIABETOLOGIA
Volume 59, Issue 3, Pages 492-501Publisher
SPRINGER
DOI: 10.1007/s00125-015-3820-4
Keywords
Gene expression; Inflammation; Insulin; Insulitis; Pancreas; T cells; Type 1 diabetes
Categories
Funding
- South-Eastern Norway Regional Health Authority
- Novo Nordisk Foundation
- Swedish Medical Research Council [VR K2011-65X-12219-15-6, K2015-54X-12219-19-4]
- Ernfors Family Fund
- Barndiabetesfonden
- Swedish Diabetes Association
- Nordic Insulin Fund
- Diabetes Wellness foundation
- RFI/VR 'SNISS' Swedish National Infrastructure
- Swedish national strategic research initiative Excellence of Diabetes Research in Sweden (EXODIAB)
- JDRF
- PEVNET Study Group - European Union's Seventh Framework Programme (FP [261441]
- Novo Nordisk Fonden [NNF14OC0010935, NNF16OC0021334] Funding Source: researchfish
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Aims/hypothesis It is thought that T cells play a major role in the immune-mediated destruction of beta cells in type 1 diabetes, causing inflammation of the islets of Langerhans (insulitis). The significance of insulitis at the onset of type 1 diabetes is debated, and the role of the T cells poorly understood. Methods In the Diabetes Virus Detection (DiViD) study, pancreatic tissue from six living patients with recent-onset type 1 diabetes was collected. The insulitis was characterised quantitatively by counting CD3(+) T cells, and qualitatively by transcriptome analysis targeting 84 T and B lymphocyte genes of laser-captured microdissected islets. The findings were compared with gene expression in T cells collected from kidney biopsies from allografts with ongoing cellular rejection. Cytokine and chemokine release from isolated islets was characterised and compared with that from islets from nondiabetic organ donors. Results All six patients fulfilled the criteria for insulitis (5-58% of the insulin-containing islets in the six patients had >= 15 T cells/islet). Of all the islets, 36% contained insulin, with several resembling completely normal islets. The majority (6183%) of T cells were found as peri-insulitis rather than within the islet parenchyma. The expression pattern of T cell genes was found to be markedly different in islets compared with the rejected kidneys. The islet-infiltrating T cells showed only background levels of cytokine/chemokine release in vitro. Conclusions/interpretation Insulitis and a significant reserve reservoir for insulin production were present in all six cases of recent-onset type 1 diabetes. Furthermore, the expression patterns and levels of cytokines argue for a different role of the T cells in type 1 diabetes when compared with allograft rejection.
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