Altered frequency and migration capacity of CD4+CD25+ regulatory T cells in systemic lupus erythematosus

Rheumatology (Oxford). 2008 Jun;47(6):789-94. doi: 10.1093/rheumatology/ken108. Epub 2008 Apr 3.

Abstract

Objectives: To determine the frequency and chemokine receptor-related migratory capacity of CD4(+)CD25(+) regulatory T cells (Tregs) and their association with clinical parameters in patients with SLE.

Methods: The expression of CD4, CD25, FoxP3 and CCR4 was examined with flow cytometry after staining with fluorescence-conjugated antibodies in 20 patients with SLE, 20 patients with RA and 21 age- and sex-matched healthy controls. For analysis of migration capacity in 24-well chemotaxis chambers, sorted cells were stimulated with ligands of CCR4, CCL17 and CCL22 and analysed with FACScan. Correlations between the number of Tregs and CCR4(+) Treg cells and clinical parameters were analysed.

Results: The numbers of Tregs(bright) and CCR4(+) Tregs(bright) were significantly decreased in the patients with SLE compared with healthy controls. The number of Tregs(bright) was negatively correlated with the levels of anti-dsDNA antibody and the number of CCR4(+) Tregs(bright) had a positive correlation with the levels of C(3). Percentage of migrated Tregs(bright) by CCL17 or CCL22 was significantly decreased in the patients with SLE compared with healthy controls.

Conclusions: These results suggest that altered frequency of Tregs and CCR4(+) Tregs(bright) and decreased migratory capacity of Tregs might be involved in the pathogenesis of SLE and indicate that targeting the Tregs can be a new therapeutic strategy in SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Chemokine CCL17 / immunology
  • Chemokine CCL22 / immunology
  • Chemotaxis, Leukocyte / immunology*
  • Female
  • Forkhead Transcription Factors / blood
  • Glucocorticoids / therapeutic use
  • Humans
  • Interleukin-2 Receptor alpha Subunit / blood
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Receptors, CCR4 / blood
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Anti-Inflammatory Agents
  • CCL17 protein, human
  • CCL22 protein, human
  • CCR4 protein, human
  • Chemokine CCL17
  • Chemokine CCL22
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoids
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, CCR4