目的：观察IL2、IL15对免疫编辑后NK细胞NKG2D的表达及其对鼻咽癌CNE2细胞杀伤活性的影响。方法：抗CD56磁珠纯化NK细胞后分为4组：（1）编辑前NK细胞组：加入100 U/ml IL2；（2）单纯编辑组：NK细胞与CNE2细胞10∶1混合，加入100U/ml IL2；（3）IL2再培养组：纯化编辑后的NK细胞，加入1 000 U/ml IL2；（4）IL15再培养组：纯化编辑后的NK细胞，加入10 ng/ml IL15。24 h后，流式细胞仪检测各组NK细胞表面NKG2D的表达；LDH释放测定法测定效靶比20∶1时各组NK细胞对CNE2细胞的杀伤活性。结果：编辑前NK细胞组、单纯编辑组、IL2再培养组、IL15再培养组NK细胞表面NKG2D的表达率分别为(97.63±0.83)%、(53.50±1.25)%、(94.47±1.00)%、(98.07±0.21)%。IL2、IL15再培养组NK细胞 NKG2D的表达分别比单纯编辑组有显著的增加（P<0.01)，该4组NK细胞对CNE2细胞的杀伤活性分别为(35.90±3.27)%、(4.70±2.30)%、(31.70±3.56)%、(40.18±2.94)%，IL2再培养组、IL15再培养组明显提高编辑后NK细胞对CNE2细胞的杀伤活性（P<0.01）， IL15的作用强于IL2。结论：高剂量IL2、IL15可以上调免疫编辑后NK细胞表面NKG2D的表达，恢复编辑后NK细胞对鼻咽癌细胞CNE2的杀伤活性，IL15的作用强于IL2。

Objective:To study the effects of IL2 and IL15 on the expression of NKG2D and the cytotoxicity of editedNK cells against human nasopharyngeal carcinoma cell line CNE2. Methods: NK cells were purified by antiCD56 MACS and were divided into four groups: noneditedNK cells group (NK cells treated with 100 U/ml IL2), editedNK cells group (NK cells cocultured with CNE2 cells at a ratio of 10∶1 and then treated with 100 U/ml IL2), editedNK cells retreated with 1 000 U/ml IL2 group, and editedNK cells retreated with 10 ng/ml IL15 group. Expression of NKG2D in each group was determined by FACS 24 h later. Cytotoxicity of NK cells against CNE2 cells (NK∶CNE2 being 20∶1) was measured by LDH releasing assay.Results: The expression of NKG2D in noneditedNK cells, editedNK cells, editedNK cells retreated with IL2, and editedNK cells retreated with IL15 were (97.63±0.83)%, (53.50±1.25)%, (94.47±1.00)%, and (98.07±0.21)%, respectively. The expression of NKG2D on editedNK cells retreated with IL2 or IL15 was significantly increased than that on editedNK cells (P<0.01). The cytotoxicity of noneditedNK cells, editedNK cells, editedNK cells retreated with IL2, and editedNK cells retreated with IL15 against CNE2 cells were (35.90±3.27)%, (4.70±2.30)%, (31.70 ±3.56)% and (40.18±2.94)%, respectively. The cytotoxicity of editedNK cells was significantly enhanced after retreated with IL2 or IL15 (P<0.01), with those retreated with IL15 being stronger than those retreated with IL2.Conclusion: High dose IL2 and IL15 can upregulate the expression of NKG2D on editedNK cells and restore their cytotoxicity against CNE2 cells, with the efficacy of IL15 stronger than that of IL2.

国家自然科学基金资助项目（No.30471663）