Systemic Lupus Erythematosus(SLE)is a prototype of autoimmune disease.Decreased cell numbers and suppressive defects of naturally occurring CD4+CD25+FOXP3 + regulatory T cells(Tregs)play an important role in the breakdown of SLE immunetolenrance.We have peviously observed significantly increased apoptosis of peripheral blood CD4+ T cells in SLE patients.Our objective here was to detect the apoptosis of Tregs in SLE patients to see if it could contribute to reduced suppressive activity of Tregs,and further elucidate the genes and signaling pathways which trigger the apoptosis in these cells.Methods and findings: The apoptosis of Tregs was evaluated in SLE patients and normal controls(NCs)by FACS.The suppressive activity of Tregs was measured by coculture with CD4+CD25-CD127dim/-T cells.The relationship of abnormal Tregs apoptosis with clinical parameters was analyzed by Pearson correlation analysis.Gene expression profiles of unstimulated Tregs from active SLE patients and NCs were generated by microarray analysis.Differential genes expression were verified by real time-PCR.We found that the Tregs from SLE patients showed a significant elevation in apoptosis and reduction in suppressive capacity compared to NCs.The increased apoptosis of Tregs was negatively correlated with the total number of Tregs and positively correlated with disease activities.Gene expression profiles of unstimulated Tregs from recent-onset SLE subjects reveal a cellular response that could make the cells sensitive to apoptosis,partially due to the stress responses and cytokine stimulation.This global picture of pathway-specific expression signatures is a step further into dissecting Tregs defects in the pathogenesis of SLE.