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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
Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för naturvetenskap och biomedicin. Högskolan i Jönköping, Hälsohögskolan, HHJ. Biomedicinsk plattform.
2009 (engelsk)Inngår i: Diabetes Metabolism Reviews, ISSN 0742-4221, E-ISSN 1099-0895, Vol. 25, nr 4, s. 335-343Artikkel i tidsskrift (Fagfellevurdert) 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. 

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2009. Vol. 25, nr 4, s. 335-343
Emneord [en]
Type 1 diabetes; high-risk children; T-helper cells; T-regulatory cells; cytokines; chemokines
HSV kategori
Identifikatorer
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
Tilgjengelig fra: 2009-06-10 Laget: 2009-06-10 Sist oppdatert: 2019-09-02bibliografisk kontrollert

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