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GAD-alum treatment ...
GAD-alum treatment induces GAD-specific CD4 T cells in a phase III clinical trial
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- Pihl, Mikael (author)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Axelsson, Stina (author)
- Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet
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- Cheramy, Mikael (author)
- Benaroya Research Institute at Virginia Mason, Seattle, USA
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- Reijonen, Helena (author)
- Benaroya Research Institute at Virginia Mason, Seattle, USA
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- Ludvgisson, Johnny (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,Barn- och ungdomskliniken i Linköping
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- Casas, Rosaura (author)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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(creator_code:org_t)
- 2013
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
Close
- Glutamic Acid Decarboxylase (GAD)65 formulated in aluminium hydroxide (GAD-alum preserved insulin secretion in a phase II clinical trial in recent onset type 1 diabetes. GADalum treated patients up-regulated FOXP3 upon antigen recall at 21 and 30 months after treatment. A 4-year follow-up of the study revealed increased frequencies of both CD25+CD127+ and CD25hiCD127lo cells in treated patients after antigen recall. A subsequent european phase III trial was closed after 15 months after failing to reach primary outcome. We monitored antigen recall induced frequencies of memory, effector and regulatory T cells throughout the phase III trial. Antigen recall induced mainly CD25+CD127+, CD45RO+ and non-suppressive FOXP3loCD45RA- cells in GAD-alum treated patients. In addition, a population of activated FSChiSSChi cells was observed, enriched in CD25+CD127+, CD45RO+ and proliferating cells. GAD65-specific T cells determined by tetramer staining were induced by antigen recall in GAD-alum treated patients and were more frequent in the FSChiSSChi population. Additional doses of GAD-alum increased frequencies of CD25+CD127+, CD45RO+ and FSChiSSChi cells but had no effect on frequencies of CD25hiCD127lo. Our findings indicate that antigen recall after GAD-alum treatment primarily induces memory and activated T cells. In particular, GAD65-specific cells were mainly of a memory or activated phenotype. Additional doses of GAD-alum mainly affect memory T cell frequency and T cell activation.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- vet (subject category)
- ovr (subject category)
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