膜型分泌型MICA对NK细胞受体NKG2D的相反调节效应及其对NK细胞受体谱的影响  

The opposite effect of mMICA and rMICA on the expression of NKG2D and the influence on NK cell receptor repertoire

作　　者：张彩[1] 冯进波 王郡甫 许晓群 张建 田志刚[3] 

机构地区：[1]山东大学医学院 [2]山东省医科院基础医学研究所 [3]中国科学技术大学免疫学研究所

出　　处：《中华微生物学和免疫学杂志》2004年第2期107-111,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家杰出青年基金资助项目(30125038);国家973资助项目(2001CB510009);国家自然科学基金重点资助项目(30230340);国家自然科学基金资助项目(30371302);国家863资助项目(2002AA216151);国家知识创新工程资助项目(KSCX2208);山东省自然科学基金资助项目(Y2002

摘　　要：目的　观察膜型和分泌型MICA对NK细胞受体表达的影响 ,以探讨NK细胞抗肿瘤活化机制及肿瘤细胞表达MICA分子的意义。方法　用MTT法测定人NK细胞系 (NK92 )的细胞毒活性 ;用RT PCR或FACS检测NK细胞受体 (NKG2D ,NKG2A B ,KIR2DL1,KIR2DS1)及NKG2D的识别配体MICA的表达。结果　肿瘤细胞表面的MICA分子可上调NKG2D的表达 ,下调抑制性受体NKG2A B和KIR2DL1的表达 ;而分泌型MICA (sMICA)分子对NKG2D及抑制性受体的表达均有抑制作用。结论　膜型MICA分子可上调NKG2D的表达 ,激发NK细胞对肿瘤细胞的细胞毒效应 ;分泌型MICA分子则通过降低NKG2D的表达下调机体的抗肿瘤免疫效应 ,肿瘤细胞分泌sMICA分子为肿瘤发生免疫逃逸的机制之一。Objective To observe the effect of mMICA and rsMICA on the expression of NK cell receptors and investigate the anti-tumor mechanisms of NK cells and the significance of MICA expression on tumor cells. Methods The cytotoxicity of human NK cells (NK92) was detected by MTT method. The expression of NK cell receptors (NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA (the ligand of NKG2D) were measured by RT-PCR or by FACS. Results The membrane MICA (mMICA) on surface of tumor cells can up-regulate the expression of NKG2D, but down-regulate the expression of inhibitory receptor NKG2A/B and KIR2DL1. The soluble MICA (sMICA) exerts negative effect on the expression of NKG2D, NKG2A/B and KIR2DL1. Conclusion mMICA can enhance the cytotoxicity of NK cells against tumor through up-regulating the expression of NKG2D. While sMICA down-regulate the immune response of NK cells by reducing the expression of NKG2D, which may promote tumor immune evasion.

关 键 词：天然杀伤细胞 细胞毒活性 MICA NK细胞受体 免疫逃逸 肿瘤细胞 

分 类 号：R392[医药卫生—免疫学]