Reduced frequency and functional defects of CD4

Background Unexplained recurrent spontaneous abortion (URSA) is defined as two or more consecutive pregnancy losses, generally of unknown cause; it is related to a failure of fetal–maternal immunological tolerance. Regulatory T cells (Tregs) exert immunosuppressive effects, which are essential to maintain fetal–maternal immunological tolerance and regulate immune balance. In this study, we used the specific cell-surface phenotype of CD4+CD25highCD127low/− Tregs to investigate the number and suppressive function of Tregs isolated from the peripheral blood of patients with URSA with the aim of expanding our understanding of their role in URSA. Methods We isolated a relatively pure population of peripheral CD4+CD25highCD127low/− Tregs and CD4+CD25− responder T cells (Tresps) from the patients with URSA and normal fertile nonpregnant control women via fluorescence-activated cell sorting. We compared the frequency, suppressive capacity, and forkhead box transcription factor P3 (FOXP3) expression of Tregs in the peripheral blood between patients with URSA and normal controls. Results The frequency of CD4+CD25highCD127low/− Tregs in the peripheral blood was lower in URSA patients than in the controls (P FOXP3 mRNA expression in Tregs was also significantly lower in the URSA patients (P P P P Conclusions We observed a lower frequency of peripheral CD4+CD25highCD127low/− Tregs with lower FOXP3 expression in the peripheral blood of URSA patients. In addition, highly purified Tregs from patients with URSA exhibited impaired suppressive effects. The defect in immune regulation in URSA patients appears to be primarily related to impaired Tregs, and not to increased resistance of Tresps to suppression. Our findings reveal a potential novel therapeutic target for URSA.