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Switch from a dominant Th1‐associated immune profile during the pre‐diabetic phase in favour of a temporary increase of a Th3‐associated and inflammatory immune profile at the onset of type 1 diabetes
Author(s) -
Ryden Anna,
Stechova Katerina,
Durilova Marianna,
Faresjö Maria
Publication year - 2009
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.958
Subject(s) - immune system , immunology , peripheral blood mononuclear cell , monokine , chemokine , tumor necrosis factor alpha , cytokine , phytohaemagglutinin , monocyte , interleukin , biology , medicine , biochemistry , in vitro
Abstract Background Type 1 diabetes (T1D) is an autoimmune disease dominated by loss of self‐tolerance resulting in depletion of the β‐cells. This study aims to confirm previous observations of a dominant T‐helper (Th)1‐like profile during the period close to onset of disease. Further, to follow the immune response from onset to 2 years duration, the study focused on spontaneous as well as autoantigen‐induced immune profile. Methods Peripheral blood mononuclear cells were collected 4 days and 1 and 2 years after diagnosis of T1D children, from healthy children carrying the human leukocyte antigen‐risk genes and from high‐risk children (ICA ≥ 20 IJDF units). Peripheral blood mononuclear cells were stimulated with glutamic acid decarboxylase (GAD 65 ) and phytohaemagglutinin (PHA). Cytokines and chemokines were detected in cell‐culture supernatants by protein microarray (naive T‐cells; interleukin (IL)‐7, Th1; interferon‐γ, tumour necrosis factor‐β, Th2; IL‐5, Th3; transforming growth factor‐β, T‐regulatory cell type 1; IL‐10 and inflammatory cytokines; tumour necrosis factor‐α, IL‐6 and chemokines; monocyte chemoattractant protein‐1, monokine upregulated by IFN‐γ) in relation to clinical outcome (C‐peptide). Results High‐risk children showed a dominant Th1‐associated profile with high spontaneous and GAD 65 ‐induced secretion. The mitogen PHA instead induced a Th2‐associated response exclusively in high‐risk children. In contrast, newly diagnosed T1D children showed a pronounced Th3‐associated cytokine profile as well as a burst of inflammatory cytokines and chemokines secreted both spontaneously and by GAD 65 and PHA stimulation. The immune response to GAD 65 and PHA, however, diminished with duration of disease. Conclusion A dominant Th1‐associated immune profile was observed during the pre‐diabetic phase. This Th1 dominance, however, diminished in favour of a temporary increase in a Th3‐associated and inflammatory immune profile at the onset of disease. Copyright © 2009 John Wiley & Sons, Ltd.