Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant

Johanna Aarnisalo, Andras Treszl, Peter Svec, Jane Marttila, Viveka Öling, Olli Simell, Mikael Knip, A. Körner, L. Madácsy, B. Vásárhelyi, Jorma Ilonen, Robert Hermann

Research output: Contribution to journalArticle

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Abstract

The 620Trp variant of the LYP protein, encoded by the lymphoid tyrosine phosphatase 22 gene (PTPN22), is associated with autoimmunity. In this study we aimed at characterising the role of this variant on lymphocyte activation. We analysed cytokine secretion and proliferation of peripheral blood mononuclear cells (PBMCs) and CD4+T cells in a cohort of clinically non-diabetic, multiple autoantibody-positive children, healthy controls and in children with type 1 diabetes (T1D). We found a decreased proliferation and IL-2 production of CD4+T cells after anti-CD3/anti-CD28 stimulation (p = 0.04 for IL-2) among T1D patients. In addition, a profoundly decreased intracellular calcium flux in CD4+T cells after PHA stimulus was detected among 620Trp carriers. In contrast, no effect of this polymorphism on tuberculin and tetanus toxoid induced PBMC proliferation and cytokine secretion was observed in autoantibody positive children, healthy controls and children with newly-diagnosed T1D. In conclusion, the LYP 620Trp variant is associated with reduced activation, proliferation and IL-2 production in CD4+T cells among T1D patients. In accordance with our previous findings on the key role of this variant on disease progression, this mechanism is likely to contribute to the development of β-cell specific autoimmunity.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalJournal of Autoimmunity
Volume31
Issue number1
DOIs
Publication statusPublished - Aug 2008

Fingerprint

Type 1 Diabetes Mellitus
Interleukin-2
T-Lymphocytes
Autoimmunity
Autoantibodies
Non-Receptor Type 22 Protein Tyrosine Phosphatase
Blood Cells
Cytokines
Tetanus Toxoid
Tuberculin
Lymphocyte Activation
Tyrosine
Disease Progression
Cell Proliferation
Calcium
Genes
Proteins

Keywords

  • Autoimmunity
  • LYP
  • PTPN22
  • T cell activation
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Aarnisalo, J., Treszl, A., Svec, P., Marttila, J., Öling, V., Simell, O., ... Hermann, R. (2008). Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant. Journal of Autoimmunity, 31(1), 13-21. https://doi.org/10.1016/j.jaut.2008.01.001

Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant. / Aarnisalo, Johanna; Treszl, Andras; Svec, Peter; Marttila, Jane; Öling, Viveka; Simell, Olli; Knip, Mikael; Körner, A.; Madácsy, L.; Vásárhelyi, B.; Ilonen, Jorma; Hermann, Robert.

In: Journal of Autoimmunity, Vol. 31, No. 1, 08.2008, p. 13-21.

Research output: Contribution to journalArticle

Aarnisalo, J, Treszl, A, Svec, P, Marttila, J, Öling, V, Simell, O, Knip, M, Körner, A, Madácsy, L, Vásárhelyi, B, Ilonen, J & Hermann, R 2008, 'Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant', Journal of Autoimmunity, vol. 31, no. 1, pp. 13-21. https://doi.org/10.1016/j.jaut.2008.01.001
Aarnisalo, Johanna ; Treszl, Andras ; Svec, Peter ; Marttila, Jane ; Öling, Viveka ; Simell, Olli ; Knip, Mikael ; Körner, A. ; Madácsy, L. ; Vásárhelyi, B. ; Ilonen, Jorma ; Hermann, Robert. / Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant. In: Journal of Autoimmunity. 2008 ; Vol. 31, No. 1. pp. 13-21.
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