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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
Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
2009 (English)In: Diabetes Metabolism Reviews, ISSN 0742-4221, E-ISSN 1099-0895, Vol. 25, no 4, p. 335-343Article in journal (Refereed) Published
Abstract [en]

Background: Type 1 diabetes (T1D) is all autoimmune disease dominated by loss of self-tolerance resulting in depletion of the beta-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-gamma, turnout necrosis factor-beta, Th2; IL-5, Th3; transforming growth factor-beta, T-regulatory cell type 1; IL-10 and inflammatory cytokines; tumour necrosis factor-alpha, IL-6 and chemokines; monocyte chemoattractant protein-1, monokine upregulated by IFN-gamma) 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 Thl-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. 

Place, publisher, year, edition, pages
John Wiley & Sons, 2009. Vol. 25, no 4, p. 335-343
Keywords [en]
Type 1 diabetes; high-risk children; T-helper cells; T-regulatory cells; cytokines; chemokines
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hj:diva-9397DOI: 10.1002/dmrr.958ISI: 000266347200008PubMedID: 19382103Scopus ID: 2-s2.0-69249202525OAI: oai:DiVA.org:hj-9397DiVA, id: diva2:222972
Available from: 2009-06-10 Created: 2009-06-10 Last updated: 2019-09-02Bibliographically approved

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Faresjö, Maria

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