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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 relationship between the expression of HLA class I molecules on the surface of tumor cells and NK killing and the regulation of IFN γ. Methods The expression of HLA-ABC molecules on the surface of 7 kinds of tumor cells was detected by indirect immunofluorescence. The target of NK killing was observed after the target cells were blocked with murine anti-human HLA ABC. After treatment of target cells with IFN γ, the surface HLA of tumor cells was observed. Changes in molecular expression and changes in NK killing. Results The proportions of HLA ABC molecules expressed in different tumor cell lines and their fluorescence intensities were all different, except for Karpas, which all showed different degrees of decline. K562 cells with negative HLA ABC expression were most sensitive to NK killing, and all other cells showed decreased sensitivity. The expression of HLA ABC molecules on the surface of tumor cells has decreased to varying degrees, and NK killing can be significantly enhanced by blocking the corresponding sites with anti-HLA monoclonal antibodies. After treated with IFN γ 500 U/ml for 48 h, the expression of HLA class I molecules on the surface of leukemia cell K562, melanoma cell M2 1 and high metastatic lung cancer cell PG was significantly increased, and the sensitivity to NK killer was decreased. After treatment with tumor Karpas, myeloid leukemia cell HL60 and colorectal cancer cell HT29, there was no significant change in the expression of HLA class I molecules, but the sensitivity to NK killing was significantly enhanced. IFNγ promotes apoptosis of HL60 and HT2 9 cells. Conclusion NK cells can recognize tumor cells with decreased or defective HLA ABC molecules and play a role in killing; IFN γ can restore the loss of HLA ABC molecules in some tumor cells, and can promote the apoptosis of some tumor cells and increase the antitumor mechanism of tumors The sensitivity.