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Characterization of resident lymphocytes in human pancreatic islets

Authors :
P.‐A. Bertilsson
P. Vickman
K. Uvebrant
J. Avartsson
Corrado M. Cilio
Malin Fex
Oskar Skog
Petter Storm
O. Korgsgren
M. Radenkovic
Luis Sarmiento
Source :
Clinical and Experimental Immunology. 187:418-427
Publication Year :
2016
Publisher :
Oxford University Press (OUP), 2016.

Abstract

Summary The current view of type 1 diabetes (T1D) is that it is an immune-mediated disease where lymphocytes infiltrate the pancreatic islets, promote killing of beta cells and cause overt diabetes. Although tissue resident immune cells have been demonstrated in several organs, the composition of lymphocytes in human healthy pancreatic islets have been scarcely studied. Here we aimed to investigate the phenotype of immune cells associated with human islets of non-diabetic organ donors. A flow cytometry analysis of isolated islets from perfused pancreases (n = 38) was employed to identify alpha, beta, T, natural killer (NK) and B cells. Moreover, the expression of insulin and glucagon transcripts was evaluated by RNA sequencing. Up to 80% of the lymphocytes were CD3+ T cells with a remarkable bias towards CD8+ cells. Central memory and effector memory phenotypes dominated within the CD8+ and CD4+ T cells and most CD8+ T cells were positive for CD69 and up to 50–70% for CD103, both markers of resident memory cells. The frequency of B and NK cells was low in most islet preparations (12 and 3% of CD45+ cells, respectively), and the frequency of alpha and beta cells varied between donors and correlated clearly with insulin and glucagon mRNA expression. In conclusion, we demonstrated the predominance of canonical tissue resident memory CD8+ T cells associated with human islets. We believe that these results are important to understand more clearly the immunobiology of human islets and the disease-related phenotypes observed in diabetes.

Details

ISSN :
13652249 and 00099104
Volume :
187
Database :
OpenAIRE
Journal :
Clinical and Experimental Immunology
Accession number :
edsair.doi.dedup.....2596f1a89500d786a9a51c3483ba0db9
Full Text :
https://doi.org/10.1111/cei.12892