Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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
Increased expression of regulatory T cell-associated markers in recent-onset diabetic children
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Show others and affiliations
2011 (English)In: Open Journal of Immunology, ISSN 2162-450X, E-ISSN 2162-4526, Vol. 1, no 3, 57-64 p.Article in journal (Refereed) Published
Abstract [en]

CD4+CD25hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as well as in a setting of possible pre-diabetic autoimmunity. Hence, the expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi T cells was analyzed using flow cytometry in 14 patients with recent onset type 1 diabetes, in 9 at-risk individuals, and 9 healthy individuals with no known risk for type 1 diabetes. Our results show there were no differences in the frequency of CD4+CD25hi cells between groups. However, compared to controls, recent-onset type 1 diabetic patients had higher expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi cells from peripheral blood. The median fluorescence intensity of FOXP3 was significantly higher in CD4+CD25hi cells from patients with type 1 diabetes than from controls. Furthermore, a positive correlation between the frequency of FOXP3+ cells and the median fluorescence intensity of FOXP3 was observed among patients with type 1 diabetes. These data suggest that the frequency of CD4+CD25hi FOXP3+ T cells in the periphery is not decreased but rather increased at onset of type 1 diabetes. Thus, functional deficiencies rather than reduced numbers of CD4+CD25hi cells could contribute to the development of type 1 diabetes. 

Place, publisher, year, edition, pages
Irvine, CA. USA: Scientific Research Publishing, 2011. Vol. 1, no 3, 57-64 p.
Keyword [en]
Regulatory T cells; Type 1 Diabetes; Autoantibodies
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-75890DOI: 10.4236/oji.2011.13007OAI: oai:DiVA.org:liu-75890DiVA: diva2:510373
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2017-12-07
In thesis
1. Reign in Blood: Immune Regulation in Type 1 Diabetes
Open this publication in new window or tab >>Reign in Blood: Immune Regulation in Type 1 Diabetes
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 1 Diabetes (T1D) is an autoimmune disease resulting in insulin deficiency as a result ofautoimmune destruction of pancreatic β-cells. Preserving β-cell function in patients with T1D would be of great benefit since patients with sustained endogenous insulin secretion are known to suffer less from secondary complications due to hyperglycemia. Glutamic acid decarboxylase 65 (GAD65) is a major autoantigen targeted by self-reactive lymphocytes in T1D, and has been used in several attempts at treating T1D by inducing tolerance to β-cell antigens. We showed positive clinical effects of GAD65 formulated with aluminium hydroxide (GAD-alum) on preservation of C-peptide secretion in a phase II clinical trial. Unfortunately, a phase III clinical trial in a larger population failed to confirm this finding. Regulatory T cells (Treg) are instrumental in maintaining peripheral tolerance to self-antigens. Deficiencies in Treg function are thought to influence the pathogenesis of autoimmune diseases, including T1D. One proposed mechanism of achieving tolerance to β-cell antigens in T1D is the induction of antigen-specific Treg through immunomodulation. The general aim of this thesis was to study immune regulation in T1D, the role of Treg and immunomodulatory effects of GAD-alum treatment in particular. Our hypothesis was that Treg biology is altered in T1D and pre-diabetes, and that an induction of GAD65-specific Treg contributes to the clinical efficacy of GAD-alum treatment. We demonstrated that T cells expressing Treg-associated markers were increased in number in patients with recent-onset T1D, as well as in children with high risk of developing T1D. We found that antigen recall 4 years after GAD-alum treatment induced cells with both regulatory and effector phenotypes in GAD-alum treated patients. Furthermore there was no effect on Treg-mediated suppression in GAD-alum treated patients, while patients with T1D, regardless of treatment, exhibited deficient Treg-mediated suppression of Teff that was intrinsic to the Treg population. We followed patients participating in a phase III trial of GAD-alum, and using an extended antibody panel we demonstrated that antigen recall induced mainly Teff cells in treated patients, along  with increased frequencies of memory T cells, non-suppressive CD45RA-FOXP3lo cells and increased GAD65-induced proliferation of mainly Teff and memory T cells. Finally we examined whether SNPs in genes encoding inflammasome components contributed to T1D risk, but found no effects of variant alleles on the risk of developing T1D, or on the efficacy of GAD-alum treatment. We show small effects on C-peptide secretion and autoantibody positivity in patients with T1D. In conclusion, we find that while Treg are deficient in patients with T1D, induction of Treg is an unlikely mechanism of action of GAD-alum treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 113 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1377
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98250 (URN)10.3384/diss.diva-98250 (DOI)978-91-7519-533-9 (ISBN)
Public defence
2013-11-08, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2013-10-04 Created: 2013-10-04 Last updated: 2013-10-07Bibliographically approved

Open Access in DiVA

fulltext(468 kB)238 downloads
File information
File name FULLTEXT01.pdfFile size 468 kBChecksum SHA-512
0843b81dd107e8a4b2aee0d2bee9c0a61989e4302b3d64a1c0379203bf56e9948bf11be9dd78d5e8a763b763f9e2af3c4ff8f21ee1f519179a3dca33bc0c1fc6
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Pihl, MikaelChéramy, MikaelMjösberg, JennyLudvigsson, JohnnyCasas, Rosaura
By organisation
PediatricsFaculty of Health SciencesClinical Immunology
In the same journal
Open Journal of Immunology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 238 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 270 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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