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High T‐helper‐1 cytokines but low T‐helper‐3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes

High T‐helper‐1 cytokines but low T‐helper‐3 cytokines, inflammatory cytokines and chemokines in... Background Type 1 diabetes (T1D) is suggested to be of T‐helper (Th)1‐like origin. However, recent reports indicate a diminished interferon (IFN)‐γ secretion at the onset of the disease. We hypothesize that there is a discrepancy in subsets of Th‐cells between children with a high risk of developing T1D, children newly diagnosed with T1D and healthy children. Methods Peripheral blood mononuclear cells (PBMC) were collected from children at high risk for T1D (islet cells antibodies (ICA) ≥ 20 IJDF‐U), those newly diagnosed and healthy children carrying the HLA‐risk gene DQB1*0302 or DQB1*0201 and DQA1*0501. Th1‐ (IFN‐γ, tumour necrosis factor (TNF)‐β, interleukin (IL)‐2), Th2‐ (IL‐4,‐5,‐13), Th3‐ (transforming growth factor (TGF‐β), IL‐10) and inflammatory associated cytokines (TNF‐α, IL‐1α,‐6) and chemokines (monocyte chemoattractant protein (MCP)‐1,‐2,‐3, Monokine unregulated by IFN‐γ (MIG), Regulated on Activation, Normal T‐cell Expressed and Secreted (RANTES), IL‐7,‐8,‐15) were detected in cell‐culture supernatants of PBMC, stimulated with glutamic acid decarboxylase 65 (GAD65) and phytohaemagglutinin (PHA), by protein micro array and enzyme linked immunospot (ELISPOT) technique. Results The Th1 cytokines IFN‐γ and TNF‐β, secreted both spontaneously and by GAD65‐ and mitogen stimulation, were seen to a higher extent in high‐risk children than in children newly diagnosed with T1D. In contrast, TNF‐α and IL‐6, classified as inflammatory cytokines, the chemokines RANTES, MCP‐1 and IL‐7 as well as the Th3 cytokines TGF‐β and IL‐10 were elevated in T1D children compared to high‐risk children. Conclusion High Th‐1 cytokines were observed in children with high risk of developing TID, whereas in children newly diagnosed with T1D Th3 cytokines, inflammatory cytokines and chemokines were increased. Thus, an inverse relation between Th1‐like cells and markers of inflammation was shown between children with high risk and those newly diagnosed with T1D. Copyright © 2007 John Wiley & Sons, Ltd. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diabetes/Metabolism: Research and Reviews Wiley

High T‐helper‐1 cytokines but low T‐helper‐3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes

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References (55)

Publisher
Wiley
Copyright
Copyright © 2007 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1520-7552
eISSN
1520-7560
DOI
10.1002/dmrr.718
pmid
17315139
Publisher site
See Article on Publisher Site

Abstract

Background Type 1 diabetes (T1D) is suggested to be of T‐helper (Th)1‐like origin. However, recent reports indicate a diminished interferon (IFN)‐γ secretion at the onset of the disease. We hypothesize that there is a discrepancy in subsets of Th‐cells between children with a high risk of developing T1D, children newly diagnosed with T1D and healthy children. Methods Peripheral blood mononuclear cells (PBMC) were collected from children at high risk for T1D (islet cells antibodies (ICA) ≥ 20 IJDF‐U), those newly diagnosed and healthy children carrying the HLA‐risk gene DQB1*0302 or DQB1*0201 and DQA1*0501. Th1‐ (IFN‐γ, tumour necrosis factor (TNF)‐β, interleukin (IL)‐2), Th2‐ (IL‐4,‐5,‐13), Th3‐ (transforming growth factor (TGF‐β), IL‐10) and inflammatory associated cytokines (TNF‐α, IL‐1α,‐6) and chemokines (monocyte chemoattractant protein (MCP)‐1,‐2,‐3, Monokine unregulated by IFN‐γ (MIG), Regulated on Activation, Normal T‐cell Expressed and Secreted (RANTES), IL‐7,‐8,‐15) were detected in cell‐culture supernatants of PBMC, stimulated with glutamic acid decarboxylase 65 (GAD65) and phytohaemagglutinin (PHA), by protein micro array and enzyme linked immunospot (ELISPOT) technique. Results The Th1 cytokines IFN‐γ and TNF‐β, secreted both spontaneously and by GAD65‐ and mitogen stimulation, were seen to a higher extent in high‐risk children than in children newly diagnosed with T1D. In contrast, TNF‐α and IL‐6, classified as inflammatory cytokines, the chemokines RANTES, MCP‐1 and IL‐7 as well as the Th3 cytokines TGF‐β and IL‐10 were elevated in T1D children compared to high‐risk children. Conclusion High Th‐1 cytokines were observed in children with high risk of developing TID, whereas in children newly diagnosed with T1D Th3 cytokines, inflammatory cytokines and chemokines were increased. Thus, an inverse relation between Th1‐like cells and markers of inflammation was shown between children with high risk and those newly diagnosed with T1D. Copyright © 2007 John Wiley & Sons, Ltd.

Journal

Diabetes/Metabolism: Research and ReviewsWiley

Published: Sep 1, 2007

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