肿瘤细胞HLAⅠ类分子表达对NK抗性的影响及IFN-γ的调节作用  

Influence of HLA class Ⅰ molecules expression on tumor cell resistance to NK lysis and the IFN-γ regulatory effect

作　　者：张彩[1] 田志刚[1] 侯桂华[2] 张建华[1] 王郡甫[1] 孙汭[1] 

机构地区：[1]山东省医学科学院基础医学研究所山东肿瘤生物治疗研究中心,济南250062 [2]山东医科大学基础医学院

出　　处：《中华肿瘤杂志》2001年第5期369-372,共4页Chinese Journal of Oncology

基　　金：国家自然科学基金资助项目 ( 39870 729;39970 82 8) ;山东省自然科学基金资助项目 (Q99C0 7)

摘　　要：目的　探讨肿瘤细胞表面HLAⅠ类分子的表达与NK杀伤的关系及IFN γ的调节作用。方法　用间接免疫荧光法检测 7种肿瘤细胞表面HLA ABC分子的表达 ;用鼠抗人HLA ABC单抗封闭靶细胞后 ,观察NK杀伤的变化 ;用IFN γ处理靶细胞后 ,观察瘤细胞表面HLA分子表达的变化及NK杀伤的变化。结果　不同肿瘤细胞株表达HLA ABC分子的比例及荧光强度均不相同 ,除Karpas外 ,均表现为不同程度的下降。HLA ABC表达阴性的K5 6 2细胞对NK杀伤最敏感 ,其他细胞的敏感性均有下降。肿瘤细胞表面HLA ABC分子的表达多有不同程度的下降 ,用抗HLA单抗封闭相应位点后 ,可使NK杀伤明显增强。用IFN γ 5 0 0U/ml处理 48h后 ,白血病细胞K5 6 2、黑色素瘤细胞M2 1和高转移肺癌细胞PG表面HLAⅠ类分子表达明显增加 ,对NK杀伤的敏感性降低 ;而人T细胞淋巴瘤Karpas、髓样白血病细胞HL6 0和结直肠癌细胞HT2 9经处理后 ,HLAⅠ类分子表达无明显变化 ,对NK杀伤的敏感性反而明显增强。IFN γ促进HL6 0和HT2 9细胞的凋亡。结论　NK细胞能识别HLA ABC分子表达下降或缺陷的肿瘤细胞并发挥杀伤作用 ;IFN γ能恢复部分肿瘤细胞HLA ABC分子的丢失 ,并能促进部分肿瘤细胞的凋亡 ,提高肿瘤对机体抗瘤机制的敏感性。Objective To investigate the relation between the NK lysis and HLA molecules expressed on the target cells as well as the regulatory effect of IFN γ.Methods The level of HLA ABC molecules on seven human tumor cell lines were detected through the indirect immune fluorescence stain. NK lysis changes were observed after the blocking of HLA molecules on the target cells with the anti HLA monoclonal antibodies or treating target cells with IFN γ.Results 1. Most of the tumor cell lines showed a complete or partial loss of HLA ABC molecules, 2. After the HLA molecules had been marked on the target cells with the anti HLA ABC antibodies, the tumor cell susceptibility to the lysis of NK cells attack increased significantly and 3. After having being treated with IFN γ 500 U/ml for more than 48 hours, the HLA ABC molecule levels on K562, M21 and PG cells went up. At the same time, their susceptibility to NK lysis was reduced. However, the resistance to Karpas, HL60 and HT29 NK lysis demonstrated a noticeable increase. The IFN γ promoted the apoptosis of HL60 and HT29 cells.Conclusion The NK cells are capable of recognizing the HLA molecules on the target cells and show no lysis in providing a negative signal with the KIRs, an effect which the anti HLA monoclonal antibodies are able to eliminate. IFN γ can be applied to make up for the loss of HLA molecules on some of the tumor cells, it can also facilitate some of the tumor cells′ apoptosis. [

关 键 词：组织相容性抗原Ⅰ类 天然杀伤细胞 干扰素-Γ 肿瘤 HLAⅠ类分子 

分 类 号：R73-36[医药卫生—肿瘤]