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Altered regulatory T cell phenotype in latent autoimmune diabetes of the adults (LADA)

Radenkovic, M. LU ; Silver, C. LU ; Arvastsson, J. LU ; Lynch, K.; Lernmark, Åke LU ; Harris, R. A.; Agardh, C. D. LU and Cilio, C. M. LU (2016) In Clinical and Experimental Immunology 186(1). p.46-56
Abstract

Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of β cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (Tregs) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating Tregs in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency (n = 39) and from healthy volunteers... (More)

Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of β cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (Tregs) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating Tregs in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency (n = 39) and from healthy volunteers (n = 20). Overall, we found the frequency and activation status of peripheral putative Tregs to be altered in LADA patients compared to healthy controls. While total T cells and CD4+ T cells expressing high levels of CD25 (CD4+CD25hi) were unchanged, the frequency and total numbers of CD4+ T cells expressing an intermediate level of CD25 (CD4+CD25int) were decreased in LADA patients. Interestingly, the expression of the Treg-specific marker forkhead box protein 3 (FoxP3), as well as the activation and memory makers CD69, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), CCR4 and CD45RO were increased in CD4+CD25+ T cells of the patients. Our data depict phenotypical changes in T cells of LADA patients that may reflect a derangement in peripheral immune regulation contributing to the slow process leading to insulin-dependent diabetes in these patients.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
autoimmunity, diabetes, regulatory T cells
in
Clinical and Experimental Immunology
volume
186
issue
1
pages
11 pages
publisher
British Society for Immunology
external identifiers
  • scopus:84991239167
  • wos:000386088500006
ISSN
0009-9104
DOI
10.1111/cei.12834
language
English
LU publication?
yes
id
7ef9a7f0-1ab4-4b7f-a835-c17fd0189b66
date added to LUP
2016-11-08 13:58:53
date last changed
2017-04-16 04:41:41
@article{7ef9a7f0-1ab4-4b7f-a835-c17fd0189b66,
  abstract     = {<p>Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of β cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (T<sub>regs</sub>) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating T<sub>regs</sub> in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency (n = 39) and from healthy volunteers (n = 20). Overall, we found the frequency and activation status of peripheral putative T<sub>regs</sub> to be altered in LADA patients compared to healthy controls. While total T cells and CD4<sup>+</sup> T cells expressing high levels of CD25 (CD4<sup>+</sup>CD25<sup>hi</sup>) were unchanged, the frequency and total numbers of CD4<sup>+</sup> T cells expressing an intermediate level of CD25 (CD4<sup>+</sup>CD25<sup>int</sup>) were decreased in LADA patients. Interestingly, the expression of the T<sub>reg</sub>-specific marker forkhead box protein 3 (FoxP3), as well as the activation and memory makers CD69, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), CCR4 and CD45RO were increased in CD4<sup>+</sup>CD25<sup>+</sup> T cells of the patients. Our data depict phenotypical changes in T cells of LADA patients that may reflect a derangement in peripheral immune regulation contributing to the slow process leading to insulin-dependent diabetes in these patients.</p>},
  author       = {Radenkovic, M. and Silver, C. and Arvastsson, J. and Lynch, K. and Lernmark, Åke and Harris, R. A. and Agardh, C. D. and Cilio, C. M.},
  issn         = {0009-9104},
  keyword      = {autoimmunity,diabetes,regulatory T cells},
  language     = {eng},
  number       = {1},
  pages        = {46--56},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Altered regulatory T cell phenotype in latent autoimmune diabetes of the adults (LADA)},
  url          = {http://dx.doi.org/10.1111/cei.12834},
  volume       = {186},
  year         = {2016},
}