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
2009 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 25, no 4, 335-343 p.Article in journal (Refereed) Published
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 andgt;= 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
2009. Vol. 25, no 4, 335-343 p.
Type 1 diabetes, high-risk children, T-helper cells, T-regulatory cells, cytokines, chemokines
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-19142DOI: 10.1002/dmrr.958OAI: oai:DiVA.org:liu-19142DiVA: diva2:223402