Abstract: Objective To investigate the possible roles of cellular immunosuppression induced by phenotypic and functional changes of peripheral CD4+CD25+ regulatory T cells （Tregs） in the pathogenesis of condylomata acuminata. Methods Three-color flow cytometry was performed to examine the expression of transcription factor Foxp3 in, along with several inhibitory membrane molecules, i.e. cytotoxic T lymphocyte associated antigen-4 （CTLA-4）, glucocorticoid-induced TNF receptor family-related gene（GITR） and programmed death-1 （PD-1） on peripheral CD4+CD25+ T cells from 46 patients with condylomata acuminata and 43 normal human controls. Meanwhile, high purity of CD4+CD25+ T cells were isolated from peripheral blood using immunomagnetic beads, and stimulated to produce intracellular suppressor cytokines such as interleukin-10 （IL-10） and transforming growth factor-beta （TGF-beta）, which were detected by flow cytometric analysis. Results The number of peripheral CD4+CD25+ Foxp3+ Tregs increased significantly in patients with condylomata acuminata than that in the normal controls （7.37% ± 2.43% vs 5.96% ± 2.09%, P < 0.001）. The expressions of CTLA-4 and PD-1 were 1.86% ± 1.13% and 2.41% ± 1.12%, respectively, in the patients, which were significantly higher than those in the normal controls（1.36% ± 0.90% and 1.70% ± 0.97%, P < 0.05 and 0.01, respectively）. The number of TGF-beta-positive CD4+CD25+ T cells from peripheral blood were increased in patients than that in the controls（1.57% ± 0.91% vs 0.78% ± 0.24%, P < 0.001）. Conclusions Human papillomavirus infection can induce the activation and proliferation of CD4+CD25+ Tregs, enhance the expression of negative costimulatory molecules and secretion of suppressor cytokines, and inhibit antiviral immune response through multiple mechanisms.