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Poor in vitro induction of FOXP3 and ICOS in type 1 cytokine environment activated T‐cells from children with type 1 diabetes
Author(s) -
Honkanen Jarno,
Skarsvik Susanne,
Knip Mikael,
Vaarala Outi
Publication year - 2008
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.904
Subject(s) - foxp3 , immune system , cytokine , type 1 diabetes , immunology , t cell , pancreatic islets , regulatory t cell , biology , il 2 receptor , medicine , islet , insulin , endocrinology , diabetes mellitus
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.