Year-end Sale % OFF 
Abstract
BackgroundUnexplained 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.MethodsWe 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.ResultsThe frequency of CD4+CD25highCD127low/− Tregs in the peripheral blood was lower in URSA patients than in the controls (P < 0.05). The mean fluorescence intensity of FOXP3 and FOXP3 mRNA expression in Tregs was also significantly lower in the URSA patients (P < 0.01). Tregs suppressed the activity of autologous Tresps stimulated with anti-CD3/CD28 beads in a concentration-dependent manner, with the strongest suppression occurring in cocultures with a 1:1 Treg:Tresp ratio in both groups; however, patient-derived Tregs exhibited a poorer capacity to suppress the proliferation of autologous Tresps than the Tregs from normal controls (P < 0.01). Moreover, Tregs isolated from URSA patients inhibited the proliferation of Tresps from normal controls less potently than the Tregs from normal controls (P < 0.01), and Tresps from URSA patients were less effectively suppressed by autologous Tregs than by those from normal controls (P < 0.01). Tresp activity were intact in both groups.ConclusionsWe 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.
Highlights
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
We observed a lower frequency of peripheral CD4+CD25highCD127low/− Regulatory T cells (Treg) with lower Forkhead box transcription factor P3 (FOXP3) expression in the peripheral blood of URSA patients
Frequency of Tregs in the peripheral blood of URSA patients The frequency of CD4+CD25highCD127low/− Tregs among CD4+ T cells in the peripheral blood was significantly lower in URSA patients (n = 60) than in the normal controls (n = 60) (4.06 ± 0.35% vs. 5.64 ± 0.49%, P < 0.05; Fig. 2)
Summary
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. Suppressive capacity, and forkhead box transcription factor P3 (FOXP3) expression of Tregs in the peripheral blood between patients with URSA and normal controls. Successful pregnancy requires various immunological adaptations to facilitate attachment, implantation, placentation, and fetal–maternal tolerance [6]. Disturbances of these adaptations are related to pregnancy complications, such as RSA and preeclampsia [7,8,9]. Tregs exert several biological effects during pregnancy; they induce decidual support for embryo implantation through contact with other immune cells [8], develop the tolerance towards paternal antigens [19, 21], and promote proper maternal vascular remodeling for robust placental development [22]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
