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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

Author:
  • Anna Ryden
  • Caroline Bolmeson
  • Carl-Oscar Jonson
  • Corrado Cilio
  • Maria Faresjo
Publishing year: 2012
Language: English
Pages: 84-96
Publication/Series: Diabetes/Metabolism Research Reviews
Volume: 28
Issue: 1
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

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.

Keywords

  • Endocrinology and Diabetes
  • soluble CTLA-4
  • PBMC
  • type 1 diabetes

Other

Published
  • Cellular Autoimmunity
  • ISSN: 1520-7552
Caroline Bolmeson
E-mail: caroline [dot] bolmeson [at] biol [dot] lu [dot] se

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