传染性单核细胞增多症患儿NKG2D表达变化初探

Preliminary study on the changes of NKG2D expression and its role in children with infectious mononu-cleosis

目的观察传染性单核细胞增多症（infectious mononucleosis，IM）患儿自然杀伤（NK）细胞和CD8＋T细胞NKG2D表达，探讨导致Epstein—Barr病毒（EBV）感染免疫功能紊乱的可能机制。方法传染性单核细胞增多症患儿29例，同龄健康对照组25例。流式细胞术检测外周血NK细胞、CD8＋T细胞表面激活性受体NKG2D及抑制性受体NKG2A表达，CDl4’单核细胞（MC）表面NKG2D配体MHCI相关分子A（MICA）与人巨细胞病毒蛋白ULl6的结合蛋白1（ULBP-1）表达；酶联免疫吸附试验（ELISA）检测血浆游离MICA（sMICA）、IL-7、IL-12、IL-15、IFN-1及TGF-p等细胞因子浓度。结果（1）IM组患儿NK细胞及CD8＋T细胞表面NKG2D表达明显低于对照组（P〈0．05），其中3例拟诊EBV-相关噬血细胞综合征（EBV-HLH）患儿表达下调最为显著；（2）IM组患儿CDl4＋MCMICA与ULBP-1表达与对照组相比差异无统计学意义（P〉O．05）；（3）IM患儿细胞因子IL-15与TGF—B较对照组降低，IL-7、IL．12、IFN-1及sMICA较对照组升高；（4）IM患儿NK细胞NKG2A表达明显高于对照组（P〈O．05），CD8’T细胞NKG2A表达与对照组相比无明显差异（P〉O．05）。结论EBV感染患儿NK细胞、CD8＋T细胞NKG2D表达过度下调可能是导致免疫功能紊乱的原因之一，IL-15及IL-12等细胞因子调控失衡，sMICA血浓度增高等多种因素可能与其NKG2D表达下调有关。

Objective To investigate the mechanism of disturbed immunological function induced by Epstein-Barr virus（EBV） infection through evaluating NKG2D expressions in NK cells and CD8＋ T lymphoeytes from children with infectious mononucleosis. Methods Twenty-nine children with infectious mononucleosis （IM） and twenty-five age-matched healthy children were enrolled in the study. NKG2D/NKG2A expressions in NK cells and CD8＋T lymphocytes, and NKG2D ligand MHC I chain-related molecules A （.MICA） and UL-16 binding proteins （ULBP-1） expressions on CD14＋ mononuclear cells （MC） were analyzed by flow cytometry. The concentrations of cytokines such as IL-7, IL-12, IL-15, IFN-γ, TGF-β and soluble MICA （sMICA） in plasma were determined by enzyme-linked immunosorbent assay （ELISA）. Results （ 1 ） Compared with the control group, NKG2D expression was significantly decreased in both NK cells and CD8＋T lymphocytes from children with IM（P〈0.05 ）, especially in the three cases of suspected EVB-HLH children. （2）There was no difference in the expression of MICA and ULBP-1 in CD14＋ MC between the children with IM and the normal control（P〉0.05）. （3）The concentrations of IL-15 and TGF-β in plasma were lower than those of the control group （P〈0.05） ,while the levels of IL-7, IL-12, IFN-~/and sMICA were up-regnlated （P〈0.05） in children with IM. （4）NKG2A expression in NKceUs in children with IM was significantly increased as compared with healthy controls（P〈0.05）, however, there was no differences in the expression of NKG2A in CD8＋ T lymphocytes between the two groups （P〉0.05）. Conclusion Remarkable down-regnlated expressions of NKG2D in NK cells and CD8＋T lymphocytes might be one of the factors causing disturbed immunological function in children with EBV infection, which might have a close relationship with abnormal cytokine milieu of IL-15 and IL-12 or high concentration of sMICA.