关键词: 疱疹,生殖器, T淋巴细胞, Foxp3, 抑制性膜分子, 细胞因子类

Abstract: Objective To investigate the phenotype and suppressive effects of peripheral blood CD4⁺CD25⁺ regulatory T cells (Tregs) on cell immunity in the pathogenesis of recurrent genital herpes (RGH).Methods The expression of transcription factor Foxp3 and inhibitory membrane molecules,e.g.,cytotoxic T lymphocyte associated antigen-4(CTLA-4),glucocorticoid-induced TNF receptor family-related gene(GITR) and programmed death-1(PD-1),were determined by three-color flow cytometry in peripheral CD4⁺CD25⁺T cells from 34 patients with RGH and 33 normal controls.Highly purified CD4⁺CD25⁺T cells were isolated ex vivo from peripheral blood by immunomagnetic beads,and the production of intracellular suppressor cytokines such as interleukin-10 (IL-10) and transforming growth factor-β(TGF-β) was tested by flow cytometry.Results The number of CD4⁺CD25⁺Foxp3⁺ Tregs increased significantly in peripheral blood of patients with RGH (9.6%±2.4%) in comparison with that of normal controls(6.4%±2.1%) (P<0.001).The expression of CTLA-4,GITR and PD-1 was significantly stronger in patients (2.8%±1.3%,12.7%±2.5% and 1.9%±1.1%,respectively) than that in controls(1.3%±1.0%,9.5%±2.4% and 1.3%±0.6%,respectively,P<0.001,P<0.001 and P<0.01,respectively).The numbers of IL-10and TGF-β-positive CD4⁺CD25⁺T cells were significantly increased in peripheral blood from patients (2.24%±0.52% and 1.29%±0.42%,respectively) compared with those from controls (1.70%±0.53% and 0.73%±0.22%,respectively,P<0.01 and P<0.001,respectively).Conclusions Herpes simplex virus infection may result in the activation and proliferation of CD4⁺CD25⁺ Tregs,expression of high level negative costimulatory molecules on the cell surface,and secretion of suppressive cytokines,which may lead to the inhibition of antiviral immune responses via multiple mechanisms.

Key words: Cytokines, Herpes,genitalis, T-lymphocytes, Foxp3, Inhibitory membrane molecules