Poor in vitro induction of FOXP3 and ICOS in type 1 cytokine environment activated T-cells from children with type 1 diabetes

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Honkanen, JarnoDepartment of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland (author)

Poor in vitro induction of FOXP3 and ICOS in type 1 cytokine environment activated T-cells from children with type 1 diabetes

Article/chapterEnglish2008

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Wiley,2008
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LIBRIS-ID:oai:DiVA.org:liu-16217
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-16217URI
https://doi.org/10.1002/dmrr.904DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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BackgroundType 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.MethodsNaive 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).ResultsChildren 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.ConclusionsThe 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.

Subject headings and genre

type 1 diabetes
T helper cells
regulatory T-cell
naive T-cell
quantitative RT-PCR
MEDICINE
MEDICIN

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Skarsvik, SusanneLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)susjo92 (author)
Knip, MikaelHospital for Children and Adolescents, University of Helsinki, Helsinki, Finland and Department of Paediatrics, Tampere University Hospital, Tampere, Finland (author)
Vaarala, OutiLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)outva41 (author)
Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, FinlandPediatrik (creator_code:org_t)

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In:Diabetes/Metabolism Research Reviews: Wiley24:8, s. 635-6411520-75521520-7560

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