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Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children

Ryden, Anna; Bolmeson, Caroline LU ; Jonson, Carl-Oscar; Cilio, Corrado LU and Faresjo, Maria (2012) In Diabetes/Metabolism Research Reviews 28(1). p.84-96
Abstract
Background High levels of soluble cytotoxic T-lymphocyte antigen 4 (soluble CTLA-4), an alternative splice form of the regulatory T-cell (Treg) associated CTLA-4 gene, have been associated with type 1 diabetes (T1D) and other autoimmune diseases, such as Grave's disease and myasthenia gravis. At the same time, studies have shown soluble CTLA-4 to inhibit T-cell activation through B7 binding. This study aimed to investigate the role of soluble CTLA-4 in relation to full-length CTLA-4 and other Treg-associated markers in T1D children and in individuals with high or low risk of developing the disease. Methods T1D children were studied at 4 days, 1 and 2 years after diagnosis in comparison to individuals with high or low risk of developing the... (More)
Background High levels of soluble cytotoxic T-lymphocyte antigen 4 (soluble CTLA-4), an alternative splice form of the regulatory T-cell (Treg) associated CTLA-4 gene, have been associated with type 1 diabetes (T1D) and other autoimmune diseases, such as Grave's disease and myasthenia gravis. At the same time, studies have shown soluble CTLA-4 to inhibit T-cell activation through B7 binding. This study aimed to investigate the role of soluble CTLA-4 in relation to full-length CTLA-4 and other Treg-associated markers in T1D children and in individuals with high or low risk of developing the disease. Methods T1D children were studied at 4 days, 1 and 2 years after diagnosis in comparison to individuals with high or low risk of developing the disease. Isolated peripheral blood mononuclear cells were stimulated with the T1D-associated glutamic acid decarboxylase 65 and phytohaemagglutinin. Subsequently, soluble CTLA-4, full-length CTLA-4, FOXP3 and TGF-beta mRNA transcription were quantified and protein concentrations of soluble CTLA-4 were measured in culture supernatant and sera. Results and Conclusions Low protein concentrations of circulating soluble CTLA-4 and a positive correlation between soluble CTLA-4 mRNA and protein were seen in T1D, in parallel with a negative correlation in healthy subjects. Further, low levels of mitogen-induced soluble CTLA-4 were accompanied by low C-peptide levels. Interestingly, low mitogen-induced soluble CTLA-4 mRNA and low TGF-beta mRNA expression were seen in high risk individuals, suggesting an alteration in activation and down-regulating immune mechanisms during the pre-diabetic phase. Copyright (C) 2011 John Wiley & Sons, Ltd. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
soluble CTLA-4, PBMC, type 1 diabetes
in
Diabetes/Metabolism Research Reviews
volume
28
issue
1
pages
84 - 96
publisher
John Wiley & Sons
external identifiers
  • wos:000298736800008
  • scopus:84855398512
ISSN
1520-7552
DOI
10.1002/dmrr.1286
language
English
LU publication?
yes
id
759f3689-4849-47eb-a7d9-f05a258131b8 (old id 2358449)
date added to LUP
2012-03-01 11:28:22
date last changed
2017-01-01 03:06:50
@article{759f3689-4849-47eb-a7d9-f05a258131b8,
  abstract     = {Background High levels of soluble cytotoxic T-lymphocyte antigen 4 (soluble CTLA-4), an alternative splice form of the regulatory T-cell (Treg) associated CTLA-4 gene, have been associated with type 1 diabetes (T1D) and other autoimmune diseases, such as Grave's disease and myasthenia gravis. At the same time, studies have shown soluble CTLA-4 to inhibit T-cell activation through B7 binding. This study aimed to investigate the role of soluble CTLA-4 in relation to full-length CTLA-4 and other Treg-associated markers in T1D children and in individuals with high or low risk of developing the disease. Methods T1D children were studied at 4 days, 1 and 2 years after diagnosis in comparison to individuals with high or low risk of developing the disease. Isolated peripheral blood mononuclear cells were stimulated with the T1D-associated glutamic acid decarboxylase 65 and phytohaemagglutinin. Subsequently, soluble CTLA-4, full-length CTLA-4, FOXP3 and TGF-beta mRNA transcription were quantified and protein concentrations of soluble CTLA-4 were measured in culture supernatant and sera. Results and Conclusions Low protein concentrations of circulating soluble CTLA-4 and a positive correlation between soluble CTLA-4 mRNA and protein were seen in T1D, in parallel with a negative correlation in healthy subjects. Further, low levels of mitogen-induced soluble CTLA-4 were accompanied by low C-peptide levels. Interestingly, low mitogen-induced soluble CTLA-4 mRNA and low TGF-beta mRNA expression were seen in high risk individuals, suggesting an alteration in activation and down-regulating immune mechanisms during the pre-diabetic phase. Copyright (C) 2011 John Wiley & Sons, Ltd.},
  author       = {Ryden, Anna and Bolmeson, Caroline and Jonson, Carl-Oscar and Cilio, Corrado and Faresjo, Maria},
  issn         = {1520-7552},
  keyword      = {soluble CTLA-4,PBMC,type 1 diabetes},
  language     = {eng},
  number       = {1},
  pages        = {84--96},
  publisher    = {John Wiley & Sons},
  series       = {Diabetes/Metabolism Research Reviews},
  title        = {Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children},
  url          = {http://dx.doi.org/10.1002/dmrr.1286},
  volume       = {28},
  year         = {2012},
}