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

• Published in: Diabetes/metabolism research and reviews Vol. 25; no. 4; pp. 335 - 343
• Main Authors: Ryden, Anna, Stechova, Katerina, Durilova, Marianna, Faresjö, Maria
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-05-2009
• Subjects: Adolescent; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; chemokines; Chemokines - blood; Chemokines - immunology; Child; Child, Preschool; cytokines; Cytokines - blood; Cytokines - immunology; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Disease Progression; Disease Susceptibility - immunology; Female; Glutamate Decarboxylase - immunology; Glutamate Decarboxylase - metabolism; high-risk children; Humans; Immune Tolerance - immunology; Longitudinal Studies; Male; MEDICIN; MEDICINE; Risk Factors; T-helper cells; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-regulatory cells; Th1 Cells - cytology; Th1 Cells - immunology; Th2 Cells - cytology; Th2 Cells - immunology; Type 1 diabetes
• ISSN: 1520-7552; 1520-7560; 1520-7560
• DOI: 10.1002/dmrr.958

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 (GAD65) 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 GAD65‐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 GAD65 and PHA stimulation. The immune response to GAD65 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.