Th1 response and systemic treg deficiency in inclusion body myositis

PLoS One. 2014 Mar 4;9(3):e88788. doi: 10.1371/journal.pone.0088788. eCollection 2014.


Objective: Sporadic inclusion body myositis (sIBM), the most frequent myositis in elderly patients, is characterized by the presence muscle inflammation and degeneration. We aimed at characterizing immune responses and regulatory T cells, considered key players in the maintenance of peripheral immune tolerance, in sIBM.

Methods: Serum and muscle tissue levels of 25 cytokines and phenotype of circulating immune cells were measured in 22 sIBM patients and compared with 22 healthy subjects. Cytokine data were analysed by unsupervised hierarchical clustering and principal components analysis.

Results: Compared to healthy controls, sIBM patients had increased levels of Th-1 cytokines and chemokines such as IL-12 (261±138 pg/mL vs. 88±19 pg/mL; p<0.0001), CXCL-9 (186±12 pg/mL vs. 13±7 pg/mL; p<0.0001), and CXCL-10 (187±62 pg/mL vs. 13±6 pg/mL; p<0.0001). This was associated with an increased frequency of CD8+CD28- T cells (45.6±18.5% vs. 13.5±9.9%; p<0.0001), which were more prone to produce IFN-γ (45.6±18.5% vs. 13.5±9.9%; p<0.0001). sIBM patients also had a decreased frequency of circulating regulatory T cells (CD4+CD25+CD127lowFOXP3+, 6.9±1.7%; vs. 5.2±1.1%, p = 0.01), which displayed normal suppressor function and were also present in affected muscle.

Conclusion: sIBM patients present systemic immune activation with Th1 polarization involving the IFN-γ pathway and CD8+CD28- T cells associated with peripheral regulatory T cell deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD28 Antigens / metabolism
  • Case-Control Studies
  • Cell Lineage / immunology
  • Cell Polarity / immunology
  • Chemokines / blood
  • Female
  • Humans
  • Immunologic Memory
  • Interferon-gamma / biosynthesis
  • Lymphocyte Count
  • Male
  • Myositis, Inclusion Body / blood
  • Myositis, Inclusion Body / immunology*
  • Myositis, Inclusion Body / pathology
  • Phenotype
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Th1 Cells / immunology*
  • Th1 Cells / pathology


  • CD28 Antigens
  • Chemokines
  • Interferon-gamma

Grant support

This work was supported by French state funds within the Investissementsd’Avenir programme under reference ANR-11-IDEX-0004-02 (LabExTransimmunom), association francaise contre les myopathies, and Société francaise nationale de medicine interne. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.