liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells and reduces CD4+ cell activation in type 1 diabetic patients
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Keyword [en]
GAD65, Immunomodulation, Immunopathology of Type 1 Diabetes
National Category
Immunology
Identifiers
URN: urn:nbn:se:liu:diva-52140OAI: oai:DiVA.org:liu-52140DiVA: diva2:279868
Available from: 2009-12-07 Created: 2009-12-07
In thesis
1. Immunological profile and aspects of immunotherapy in type 1 diabetes
Open this publication in new window or tab >>Immunological profile and aspects of immunotherapy in type 1 diabetes
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 1 diabetes (T1D) is a chronic, autoimmune disease caused by a T cell mediated attack on the insulin producing pancreatic ß-cells. Even though reasonable quality of life can be acquired with modern insulin therapy, prevention of acute and late serious complications is facilitated by preservation of residual insulin secretion. Preventing β-cell destruction is therefore an important goal of T1D therapy. Characterisation of immunological changes in the course of T1D is essential for understanding the underlying pathogenic mechanisms and for evaluating the efficacy of therapeutic intervention.

 

This thesis aimed to study the immune profile in individuals at increased risk of T1D and in patients diagnosed with the disease. In addition, the immunological effects of treatment with the B vitamin, Nicotinamide, and by antigen-specific immunotherapy using GAD65, have been studied in high-risk individuals and in T1D patients, respectively.

We have found that individuals at high risk of T1D had an increased T helper (Th) 1 like immune profile, defined by high secretion of interferon (IFN) -γ. At the time of clinical onset of T1D, the Th1 dominance was diminished. We further demonstrate that children with newly diagnosed T1D had a suppressed Th1 like profile, detected by chemokine and chemokine receptor profile. This was accompanied by an induced population of CCR7+ and CD45RA+ naïve, CD8+cytotoxic T (Tc) cells and a reduced CD45RO+ memory Tc cell pool.

 

It has previously been shown that oral Nicotinamide had no clinical effect in prevention of T1D. However, we found that the treatment was associated with a decreased secretion of IFN-γ. We have previously shown that subcutaneous injections with GAD-alum in T1D children induced a better preservation of endogenous insulin secretion compared with placebo. Here, we demonstrate that the treatment induced an early antigen-specific Th2 and regulatory immune profile. After a few months, and still after more than two years, the recall response to GAD65 was characterised by a broader range of cytokines. GAD-alum treatment also induced a GAD65-specific CD4+CD25highFOXP3+ cell population and reduced the levels of CD4+CD25+ cells.

 

In conclusion, a Th1 like immune profile in pre-diabetic individuals indicates an imbalance of the immune system. At time of clinical onset, and in the period afterwards, reduction of the Th1 associated immune response could be an effect of a suppressed destructive process, selective recruitment of effector T cells to the pancreas or a defective immune regulation. The protective effect of GAD-alum in T1D children seems to be mediated by an early skewing of GAD65-induced responses towards a Th2 phenotype. Further, induction of GAD65-specific T cells with regulatory characteristics might be able to suppress autoreactive responses and inflammation in the pancreas.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 82 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1161
National Category
Immunology
Identifiers
urn:nbn:se:liu:diva-52139 (URN)978-91-7393-467-1 (ISBN)
Public defence
2010-01-14, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2010-01-24 Created: 2009-12-07 Last updated: 2010-01-25Bibliographically approved

Open Access in DiVA

No full text

By organisation
Pediatrics Pediatrics
Immunology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 55 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf