Reducti on of T cell receptor diversity in NOD mice prevents development of type 1 diabetes but not Sjögren's syndrome

Joanna Kern, Robert Drutel, Silvia Leanhart, Marek Bogacz, Rafal W Pacholczyk

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Non-obese diabetic (NOD) mice are well-established models of independently developing spontaneous autoimmune diseases, Sjögren's syndrome (SS) and type 1 diabetes (T1D). The key determining factor for T1D is the strong association with particular MHCII molecule and recognition by diabetogenic T cell receptor (TCR) of an insulin peptide presented in the context of I-A g7 molecule. For SS the association with MHCII polymorphism is weaker and TCR diversity involved in the onset of the autoimmune phase of SS remains poorly understood. To compare the impact of TCR diversity reduction on the development of both diseases we generated two lines of TCR transgenic NOD mice. One line expresses transgenic TCRβ chain originated from a pathogenically irrelevant TCR, and the second line additionally expresses transgenic TCRαmini locus. Analysis of TCR sequences on NOD background reveals lower TCR diversity on Treg cells not only in the thymus, but also in the periphery. This reduction in diversity does not affect conventional CD4+ T cells, as compared to the TCRmini repertoire on B6 background. Interestingly, neither transgenic TCRβ nor TCRmini mice develop diabetes, which we show is due to lack of insulin B:9-23 specific T cells in the periphery. Conversely SS develops in both lines, with full glandular infiltration, production of autoantibodies and hyposalivation. It shows that SS development is not as sensitive to limited availability of TCR specificities as T1D, which suggests wider range of possible TCR/peptide/MHC interactions driving autoimmunity in SS.

Original languageEnglish (US)
Article numbere112467
JournalPloS one
Volume9
Issue number11
DOIs
StatePublished - Nov 7 2014

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Inbred NOD Mouse
insulin-dependent diabetes mellitus
Medical problems
T-Cell Antigen Receptor
Type 1 Diabetes Mellitus
T-lymphocytes
receptors
mice
genetically modified organisms
T-cells
T-Cell Antigen Receptor Specificity
T-Lymphocytes
Association reactions
Xerostomia
Peptides
Thymus
Molecules
Regulatory T-Lymphocytes
Autoimmunity
Autoantibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Reducti on of T cell receptor diversity in NOD mice prevents development of type 1 diabetes but not Sjögren's syndrome. / Kern, Joanna; Drutel, Robert; Leanhart, Silvia; Bogacz, Marek; Pacholczyk, Rafal W.

In: PloS one, Vol. 9, No. 11, e112467, 07.11.2014.

Research output: Contribution to journalArticle

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