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γ干扰素对人NK细胞识别功能的负调节作用
作者姓名:Zhang C  Tian ZG  Zhang J  Feng JB  Zhang JH  Xu XQ
作者单位:1. 250012,济南,山东大学药学院
2. 230027,合肥,中国科学技术大学生命科学院免疫学研究所
3. 山东省医学科学院基础医学研究所
基金项目:国家自然科学基金重点资助项目(3 0 2 3 0 3 40 ),国家自然科学基金资助项目(3 0 3 713 0 2),国家863资助项目 (2 0 0 2AA2 1615 1),国家973资助项目(2 0 0 1CB5 10 0 0 9),国家杰出青年基金资助项目(3 0 12 5 0 3 8),国家知识创新工程资助项目(KSCX2 2 0 8)
摘    要:目的 探讨γ干扰素(IFN-γ)对人NK细胞识别功能的负调节作用。方法 用MTT法测定人NK细胞系(NK92,NKL)的细胞毒活性及细胞增殖能力;用RT-PCR检测NK细胞受体(NKG2D、NKG2A/B、KIR2DLI、KIR2DSI)及NKG2D的识别配体主要组织相容性复合体Ⅰ类链相关分子A(MICA)的表达。结果 NK细胞系(NK92、NKL)对MICA表达阳性的肿瘤细胞杀伤活性明显高于对MICA表达阴性者;IFN-γ 1000U/ml以上可明显抑制NK细胞对MICA表达阳性肿瘤细胞的细胞毒活性,并轻度抑制NK细胞的增殖,而对MICA表达阴性肿瘤细胞的杀伤活性无明显抑制作用;IFN-γ可抑制NK细胞系活化受体NKG2D的表达,增强抑制性受体NKG2A/B和KIR2DLI的表达。结论 IFN-γ可能通过下调NK细胞活化受体的表达,上调抑制性受体的表达,使NK识别的信号平衡向抑制性方向倾斜,从而对NK细胞功能发挥负调节作用,这种作用可能是NK细胞自我调节功能的表现。

关 键 词:γ干扰素  NK细胞  识别功能  负调节作用  IFN-γ  肿瘤细胞

The negative regulatory effect of IFN-gamma on cognitive function of human natural killer cells
Zhang C,Tian ZG,Zhang J,Feng JB,Zhang JH,Xu XQ.The negative regulatory effect of IFN-gamma on cognitive function of human natural killer cells[J].Chinese Journal of Oncology,2004,26(6):324-327.
Authors:Zhang Cai  Tian Zhi-gang  Zhang Jian  Feng Jin-bo  Zhang Jian-hua  Xu Xiao-qun
Institution:Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Abstract:OBJECTIVE: To investigate the regulatory effect of IFN-gamma on recognition of target cells by human natural killer (NK) cells. METHODS: The cytotoxic activity of human NK cell lines (NK92, NKL) was detected by MTT method. Expression of NK cell receptors (NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA on target cells (the ligand of NKG2D) was measured by RT-PCR. RESULTS: Both NK92 and NKL cells exerted higher cytotoxicity to tumor cells with MICA expression, while tumors without MICA expression could resist NK cell lysis. IFN-gamma (> 1000 U/ml) inhibited NK lysis of tumor cells with MICA expression through down-regulating the expression of NKG2D, but up-regulating the expression of NKG2A/B and KIR2DL1. CONCLUSION: IFN-gamma has a negative effect on activation and cytotoxicity of human NK cells by altering the balance between the expression of activating and inhibitory receptors on NK cells in favor of inhibition. This may serve to limit NK cell over-activation in vivo.
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