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Characterization of resident lymphocytes in human pancreatic islets

Radenkovic, M. LU ; Uvebrant, K; Skog, O.; Sarmiento-Pérez, Luis LU ; Avartsson, J.; Storm, P. LU ; Vickman, P.; Bertilsson, P. A. LU ; Fex, M. LU and Korgsgren, O., et al. (2017) In Clinical and Experimental Immunology 187(3). p.418-427
Abstract

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... (More)

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.

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publication status
published
subject
keywords
diabetes, human, memory, pancreas, T cells
in
Clinical and Experimental Immunology
volume
187
issue
3
pages
10 pages
publisher
British Society for Immunology
external identifiers
  • scopus:85011339247
  • wos:000393976800010
ISSN
0009-9104
DOI
10.1111/cei.12892
language
English
LU publication?
yes
id
3429eac0-74f6-4110-8226-21614282423d
date added to LUP
2017-02-16 15:51:41
date last changed
2018-04-15 04:41:04
@article{3429eac0-74f6-4110-8226-21614282423d,
  abstract     = {<p>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<sup>+</sup> T cells with a remarkable bias towards CD8<sup>+</sup> cells. Central memory and effector memory phenotypes dominated within the CD8<sup>+</sup> and CD4<sup>+</sup> T cells and most CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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.</p>},
  author       = {Radenkovic, M. and Uvebrant, K and Skog, O. and Sarmiento-Pérez, Luis and Avartsson, J. and Storm, P. and Vickman, P. and Bertilsson, P. A. and Fex, M. and Korgsgren, O. and Cilio, C. M.},
  issn         = {0009-9104},
  keyword      = {diabetes,human,memory,pancreas,T cells},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {418--427},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Characterization of resident lymphocytes in human pancreatic islets},
  url          = {http://dx.doi.org/10.1111/cei.12892},
  volume       = {187},
  year         = {2017},
}