CD4～+CD25～+ Regulatory T Cells In Peripheral Blood Of Patients With Ankylosing Spondylitis

Objective: The present study aims to characterize and quantify the CD4+CD25+ regulatory T cell population in the peripheral blood of patients with ankylosing spondylitis (AS) and to determine the possible influence of treatments.Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 25 active AS patients, 19 stable AS patients treated with etanercept, thalidomide or sulfasalazine, and 21 healthy subjects respectively. CD4+CD25high T cells were analyzed using flow cytometry, and mRNA expression of FOXP3 was determined by real-time PCR. Proliferation of T cells to PHA was measured by WST-1 assay using depleted CD25+ cells by immunomagnetic sorting.Results: There were no significant differences in the percentage of CD4+CD25high cells in peripheral blood between patients with active AS and controls. However, PBMC from patients with active AS expressed reduced levels of FOXP3 mRNA which were inversely correlated with C-reactive protein. Moreover, CD4+CD25+ cells in AS patients exhibited declined suppressive capacity on the proliferation of effector T cells in vitro. Treatment with etanercept or thalidomide increased CD4+CD25high cells and FOXP3 mRNA expression in the peripheral blood of AS patients.Conclusion: These results demonstrate that a defective FOXP3-expressing CD4+CD25+ regulatory T cell population may contribute to the occurrence and progression of AS. Up-regulation of CD4+CD25+ regulatory T cells by inhibiting TNF-αis likely to be a potential mechanism for clinical efficacy of anti-TNF therapy and thalidomide.