复发性生殖器疱疹患者外周血NK细胞受体和共刺激分子的表达

Expression of activating and inhibitory receptors as well as costimulatory molecules on peripheral blood natural killer cells in patients with recurrent genital herpes

目的探讨NK细胞表面激活性受体（NKG2D、NKp46）和抑制性受体（NKG2A、KIR）以及共刺激分子（OX40、4—1BB、ICOS）的表达在复发性生殖器疱疹（RGH）发病中的作用。方法采用四色免疫荧光抗体染色，经流式细胞仪检测44例RGH患者外周血NK细胞表达NKG2D、NKp46、NKG2A、KIR的水平及29例RGH患者NK细胞上OX40、4—1BB、ICOS分子表达。结果RGH患者外周血NK细胞表达激活性受体NKG2D和NKp46的百分比分别为（93．3±5．4）％和（88．9±8．7）％，均显著低于对照组的（96．9±2．5）％和（93．4±4．1）％，P值分别〈0．01。抑制性受体NKG2A、KIR的表达水平差异均无统计学意义（P〉0．05）。共刺激分子OX40表达下调，患者和对照组分别为（1．0±1．1）％和（1．8±1．7）％（P〈0．05）。结论单纯疱疹病毒感染能下调NK细胞激活性受体及共刺激分子表达，抑制NK细胞的活化，使病毒感染细胞逃逸NK细胞的天然杀伤作用。

Objective To investigate the expression of activating receptors （NKG2D and NKp46）, inhibitory receptors （NKG2A and KIR） as well as costimulatory molecules （OX40, 4-1BB and ICOS） on peripheral blood natural killer （NK） cells from patients with recurrent genital herpes （RGH）. Methods Four-color immunofluorescence staining with flow cytometry was used to detect the expression of NKG2D, NKG2A, KIR and NKp46 in 44 patients with RGH and 40 normal human controls, and to detect the expression of OX40, 4-1BB and ICOS in 29 patients with RGH and 29 normal human controls. Results The proportions of NKG2D-positive and NKp46-positive NK cells significantly decreased in patients with RGH than those in the normal human controls [（93.3 ± 5.4）% vs （96.9 ± 2.5）%, （88.9 ± 8.7）% vs（93.4± 4.1）%, respectively, both P 〈 0.01]. Between the patients and controls, no significant difference was observed in the expression of NK cell inhibitory receptors, NKG2A E （41.8 ± 14.4）% vs （46.0 ± 14.7）%, P 〉 0.051 or KIR [（68.3 ± 19.1）% vs （69.1± 17.6）%, P 〉 0.05]. A lower expression of costimulatory molecule OX40 was noted in NK cells from patients with RGH compared with those in normal controls [（1.0 ± 1.1）% vs （1.8 ±1.7）%, P 〈 0.05]. Conclusions Herpes simplex virus infection could down-regulate the expression of NK cell activating receptors and costimulatory molecules, subsequently suppress the activation of NK cells, and lead to the escape of virus-infected cells from the killing of NK cells.