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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(s) -
Rydén Anna,
Bolmeson Caroline,
Jonson CarlOscar,
Cilio Corrado M.,
Faresjö Maria
Publication year - 2012
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1286
Subject(s) - phytohaemagglutinin , peripheral blood mononuclear cell , ctla 4 , foxp3 , immunology , cytotoxic t cell , antigen , immune system , biology , t cell , medicine , endocrinology , biochemistry , in vitro
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‐β 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‐β mRNA expression were seen in high risk individuals, suggesting an alteration in activation and down‐regulating immune mechanisms during the pre‐diabetic phase. Copyright © 2011 John Wiley & Sons, Ltd.