Rheumatology Advance Access originally published online on April 3, 2008
Rheumatology 2008 47(6):789-794; doi:10.1093/rheumatology/ken108
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Altered frequency and migration capacity of CD4+CD25+ regulatory T cells in systemic lupus erythematosus
1Department of Internal Medicine and 2Department of Orthopedic Surgery, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, Jeonbuk, Korea.
Correspondence to: W.-H. Yoo, Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, #634-18, Geumam-Dong, Deokjin-Gu, Jeonju, Jeonbuk 561–712, Korea. E-mail: ywhim{at}chonbuk.ac.kr
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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 Tregsbright and CCR4+ Tregsbright were significantly decreased in the patients with SLE compared with healthy controls. The number of Tregsbright was negatively correlated with the levels of anti-dsDNA antibody and the number of CCR4+ Tregsbright had a positive correlation with the levels of C3. Percentage of migrated Tregsbright 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+ Tregsbright 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.
KEY WORDS: Regulatory T lymphocytes, Systemic lupus erythematosus, CCR4, Cell migration
* H.-Y. Lee and Y.-K. Hong equally contributed to this work.
Submitted 28 November 2007; Accepted 13 February 2008