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Regulatory T cell p...
Regulatory T cell phenotype and function 4 years after GAD–alum treatment in children with type 1 diabetes
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- Pihl, Mikael (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Åkerman, Linda (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Axelsson, Stina (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Chéramy, Mikael (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Hjorth, Maria (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Mallone, R. (författare)
- St Vincent Paul Hospital, France
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- Ludvigsson, Johnny (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Pediatrik,Hälsouniversitetet,Barn- och ungdomskliniken i Linköping
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- Casas, Rosaura (författare)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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(creator_code:org_t)
- 2013-04-18
- 2013
- Engelska.
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Ingår i: Clinical and Experimental Immunology. - : Wiley-Blackwell. - 0009-9104 .- 1365-2249. ; 172:3, s. 394-402
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://www.ncbi.nlm...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- CD4 T cells (T helper
- Th0
- Th1
- Th2
- Th3
- Th17)
- diabetes
- immune regulation
- regulatory T cells (Treg)
- therapy/immunotherapy
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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