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. 2016 Mar;59(3):492-501.
doi: 10.1007/s00125-015-3820-4. Epub 2015 Nov 24.

Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes

Lars Krogvold  1   2 , Anna Wiberg  3 , Bjørn Edwin  4   5 , Trond Buanes  4   6 , Frode Lars Jahnsen  7   8 , Kristian F Hanssen  4   9 , Erik Larsson  3 , Olle Korsgren  3 , Oskar Skog  3 , Knut Dahl-Jørgensen  10   4
Affiliations

Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes

Lars Krogvold et al. Diabetologia. 2016 Mar.

Abstract

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 non-diabetic 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 (61-83%) 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.

Keywords: Gene expression; Inflammation; Insulin; Insulitis; Pancreas; T cells; Type 1 diabetes.

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