Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2358449
- author
- Ryden, Anna ; Bolmeson, Caroline LU ; Jonson, Carl-Oscar ; Cilio, Corrado LU and Faresjo, Maria
- organization
- publishing date
- 2012
- 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 Inc.
- external identifiers
-
- wos:000298736800008
- scopus:84855398512
- pmid:22218756
- 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
- 2016-04-01 09:55:10
- date last changed
- 2022-01-25 17:58:30
@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}},
keywords = {{soluble CTLA-4; PBMC; type 1 diabetes}},
language = {{eng}},
number = {{1}},
pages = {{84--96}},
publisher = {{John Wiley & Sons Inc.}},
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}},
doi = {{10.1002/dmrr.1286}},
volume = {{28}},
year = {{2012}},
}