Objective To compare frequencies of natural killer (NK) cell subsets and their surface expression of the NKG2D receptor in patients with primary biliary cirrhosis (PBC),and to determine the correlation between expression of MICA on monocytes and function-associated receptors on the NK cells of PBC patients.Methods Twenty patients with PBC and 18 healthy donors were included in the study.Peripheral blood samples anticoagulated with heparin were labeled with the following antibody combinations:anti-CD45/anti-CD14/anti-MICA,antiCD3/anti-CD56/anti-CD16/anti-NKG2D.Frequencies of MICApositive monocytes,NK cell subsets,and NK cells with surface expression of NKG2D were measured with flow cytometry.Correlation of MICA expression on monocytes with NKG2D expreesion on NK cells was assessed through linear correlation and regression analysis.Results The PBC patients had significantly lower percentages of NK cells than the healthy donors (6.8％±2.9％ vs.16.4％±3.4％,P =0.000 ＜ 0.05).In the PBC patients,the percentage of CD56-positive NK ceils was significantly higher than that of CD16-positive NK cells (4.2％±2.8％ vs.1.4％±0.7％,P =0.003 ＜ 0.05).The PBC patients also had significantly higher percentage of NKG2D surface expressing CD56-positive NK cells than the healthy donors (79.4％±10.2％ vs.64.8％±10.7％,P =0.000 ＜ 0.05).The PBC patients and healthy donors showed no statistically significant differences in percentages of NKG2D surface expressing CDl6-positive NK (70.1％±12.9％ vs.61.1％±5.9％,P =0.078 ＞ 0.05).MICA was seldom detected on normal monocytes(2.6％±1.9％),but present for 51.6％±16.2％ of monoeytes from the PBC patients (P =0.000 ＜ 0.05).There was a significant difference in frequency of CD14/MICA double-positive monocytes between the healthy donors and PBC patients.No correlation of MICA expression on monocytes with NKG2D expression on NK cells was found.Conclusion PBC patients have lower levels of NK cells in peripheral blood than their healthy counterparts.PBC patients also have higher levels of the CD56+ NK cell subset and cells with surface expression of the activated NKG2D receptor.It appears that PBC patients have a greater level of CD14+MICA+ peripheral blood mononuclear cells.NK cells may be affected by the PBC-related monocytes and participate in disease pathogenesis through immune regulation.%目的 研究原发性胆汁性肝硬化患者外周血自然杀伤(NK)细胞亚群、NKG2D及单核细胞MIC表达情况,探讨原发性胆汁性肝硬化(PBC)时NK细胞激活的机制,为寻找PBC新的治疗靶点提供理论依据. 方法 PBC患者20例(PBC组),健康体检者18名(对照组),比较肝生物化学指标、免疫学指标,流式细胞仪检测外周血NK细胞亚群比例及各亚群表面NKG2D的表达、单核细胞表面MICA表达情况.直线相关分析单核细胞MICA表达频率与NK细胞表达NKG2D频率的关联性. 结果 PBC患者外周血NK细胞低于正常对照组(PBC组比对照组:6.8％±2.9％比16.4％±3.4％,P＜0.05);以CD56+NK亚群为主(CD56+NK比CD16+NK:4.2％±2.8％比1.4％±0.7％);CD56+NK细胞表面NKG2D受体呈高表达(PBC组比对照组79.4％±10.2％比64.8％±10.7％,P＜0.05),而CD16+NK细胞NKG2D表达无明显变化(PBC组比对照组:70.1％±12.9％比61.1％±5.9％,P＞0.05).PBC组单核CD14+MICA+细胞增多(PBC组比对照组:51.6％±16.2％比2.6％±1.9％,P＜0.05).CD14+MICA与NK细胞NKG2D表达无明显相关性(CD14+MICA比CD56+NK NKG2D.r=-0.32,P＞0.05;CD14+MICA比CD16+NK-NKG2D:r=-0.27,P＞ 0.05).结论 PBC患者外周血中NK细胞下降.NK细胞以CD56+NK亚群为主且高表达其活化受体NKG2D,同时外周血CD14+MICA+单核细胞异常增生.提示NK细胞可能受单核细胞活化并通过发挥免疫调节作用参与PBC发病.
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