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Regulatory T cell p...
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Pihl, MikaelLinköpings universitet,Pediatrik,Hälsouniversitetet
(author)
Regulatory T cell phenotype and function 4 years after GAD–alum treatment in children with type 1 diabetes
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013-04-18
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Wiley-Blackwell,2013
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-93379
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-93379URI
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https://doi.org/10.1111/cei.12078DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies|Swedish Research Council|K2008-55x-20652-01-3|Swedish Child Diabetes Foundation (Barndiabetesfonden)||Medical Research Council of Southeast Sweden||JDRF|1-2008-106|Ile-de-France CODDIM||Inserm Avenir Program||
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Glutamic acid decarboxylase (GAD)65 formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. In addition, GAD-alum treated patients increased CD4+CD25hi forkhead box protein 3+ (FoxP3+) cell numbers in response to in-vitro GAD65 stimulation. We have carried out a 4-year follow-up study of 59 of the original 70 patients to investigate long-term effects on the frequency and function of regulatory T cells after GAD-alum treatment. Peripheral blood mononuclear cells were stimulated in vitro with GAD65 for 7 days and expression of regulatory T cell markers was measured by flow cytometry. Regulatory T cells (CD4+CD25hiCD127lo) and effector T cells (CD4+CD25–CD127+) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. GAD-alum-treated patients displayed higher frequencies of in-vitro GAD65-induced CD4+CD25+CD127+ as well as CD4+CD25hiCD127lo and CD4+FoxP3+ cells compared to placebo. Moreover, GAD65 stimulation induced a population of CD4hi cells consisting mainly of CD25+CD127+, which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). Assessment of suppressive function in expanded regulatory T cells revealed no difference between GAD-alum- and placebo-treated individuals. Regulatory T cell frequency did not correlate with C-peptide secretion throughout the study. In conclusion, GAD-alum treatment induced both GAD65-reactive CD25+CD127+ and CD25hiCD127lo cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment.
Subject headings and genre
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CD4 T cells (T helper
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Th0
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Th1
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Th2
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Th3
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Th17)
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diabetes
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immune regulation
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regulatory T cells (Treg)
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therapy/immunotherapy
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Åkerman, LindaLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)linak20
(author)
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Axelsson, StinaLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)stiax77
(author)
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Chéramy, MikaelLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)mikch88
(author)
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Hjorth, MariaLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)marhe44
(author)
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Mallone, R.St Vincent Paul Hospital, France
(author)
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Ludvigsson, JohnnyÖstergötlands Läns Landsting,Linköpings universitet,Pediatrik,Hälsouniversitetet,Barn- och ungdomskliniken i Linköping(Swepub:liu)johlu29
(author)
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Casas, RosauraLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)rosca56
(author)
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Linköpings universitetPediatrik
(creator_code:org_t)
Related titles
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In:Clinical and Experimental Immunology: Wiley-Blackwell172:3, s. 394-4020009-91041365-2249
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