Abstract
Background
Type 1 diabetes (T1D) is characterised by loss of tolerance to beta‐cell antigens, and the insulin‐producing beta‐cells in the pancreatic islets are destroyed by the host's own immune system. Immunological risk factors associated with T1D are related to the defects in the polarization of T‐cells and in the function of regulatory T (Treg)‐cells. We set out to study whether an impaired induction of regulatory mechanisms during the generation of T‐cell responses upon stimulation is associated with T1D.
Methods
Naive T‐cells were isolated from 18 children with recent T1D (0–14days from diagnosis; mean age 9.3 years), 11 children who had had T1D for at least 1 year (mean age 10.6) and 14 non‐diabetic children (mean age 8.1). CD45RA+ T‐cells were stimulated with PHA for 72 h in type 1 cytokine [interleukin (IL)‐12 and anti‐IL‐4] or type 2 cytokine (IL‐4 and anti‐IL‐12) environment. T‐cell polarization and regulation related markers were analysed by quantitative reverse transcription polymerase chain reaction (QRT‐PCR) (Th1 promoting T‐bet, Th2 promoting GATA‐3 and regulation related FOXP3, ICOS and NFATc2).
Results
Children with recently diagnosed T1D showed decreased induction of FOXP3, ICOS and NFATc2 in T‐cells activated in type 1 cytokine milieu (p = 0.007, p = 0.001, and p = 0.02), whereas no differences between the diabetic and healthy children were seen in the up‐regulation of activation markers, T‐bet and GATA‐3.
Conclusions
The poor induction of factors that mediate down‐modulation of T‐cell responses upon stimulation in type 1 cytokine environment may contribute to the development of autoreactive type 1 responses in T1D. Copyright © 2008 John Wiley & Sons, Ltd.