Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes
2016 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 3, 492-501 p.Article in journal (Refereed) Published
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.
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.
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.
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.
Place, publisher, year, edition, pages
2016. Vol. 59, no 3, 492-501 p.
Gene expression; Inflammation; Insulin; Insulitis; Pancreas; T cells; Type 1 diabetes
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:uu:diva-274977DOI: 10.1007/s00125-015-3820-4ISI: 000377302900012PubMedID: 26602422OAI: oai:DiVA.org:uu-274977DiVA: diva2:898049
FunderNovo NordiskSwedish Child Diabetes FoundationSwedish Diabetes Association
De två första författarna delar förstaförfattarskapet.
De två sista författarna delar sistaförfattarskapet.2016-01-272016-01-272016-10-06Bibliographically approved