人肿瘤细胞T_H2类细胞因子的逆转与NK抗性变化的研究

The switching of T H2 cytokines to T H1 cytokines and their changes of resistibility of human tumor cells to NK

目的研究促使人肿瘤细胞中ＴＨ２类细胞因子表达向ＴＨ０型的逆转及逆转后的肿瘤细胞对ＮＫ抗性的变化。方法首先用ＭＴＴ方法对悬浮培养的肿瘤细胞株ＤＢ大淋巴细胞瘤、Ｋａｒｐａｓ淋巴瘤、Ｍｉｃｈａｅｌ淋巴瘤、Ｒａｊｉ、ＨＬ６０和Ｋ５６２进行了ＮＫ杀伤敏感性的筛选。选择ＮＫ不敏感的Ｋａｒｐａｓ淋巴瘤和ＨＬ６０，用ｒｈＩＦＮγ、ｒｈＩＬ－１２和抗ＩＬ－１０ＭｃＡｂ经不同组合对其进行由ＴＨ２类细胞因子表达向ＴＨ１类细胞因子表达的促逆转研究，并观察促逆转后的肿瘤细胞对ＮＫ抗性的变化。结果ＲＴ－ＰＣＲ结果表明，经上述不同细胞因子组合诱导后，Ｋａｒｐａｓ淋巴瘤细胞均从表达ＴＨ２类细胞因子为主向ＴＨ０型逆转，并且各组逆转后的肿瘤细胞对ＮＫ的抗性均有不同程度的减弱。结论ＴＨ１类细胞因子（如ＩＦＮγ）、ＴＨ２类细胞因子拮抗剂（如ＩＬ－１０单抗）和ＩＬ－１２不同程度地促进肿瘤细胞表达的细胞因子由ＴＨ２型向ＴＨ０／ＴＨ１型逆转。促逆转后可以改善肿瘤细胞对机体杀伤作用的敏感性。

Objective To study the switching of tumor cells from T H2 to T H0,and their changes of resistibility of tumor cells to NK. Methods First we analyzed the sensitivity of DB large cell lymphoma,Karpas lymphoma, Michael lymphoma,Raji, HL60 and K562 (as control) to human NK cytotoxicity by MTT colorimetric method. Karpas lymphoma and HL60 were then to be checked the change of NK resistance after switching, from T H2 type to T H0/T H1 type by various cytokines. Results RT PCR indicated that Karpas lymphoma cells induced with different cytokines were all switched from the expression of T H2 cytokines to T H0 type. Conclusions Our results suggest that T H1 type cytokines(e.g.IFNγ),T H2 type antagonist (e.g.IL 10 McAb) and IL 12 can change the cytokine pattern of tumor cells from T H2 type to T H0/T H1 in varying degrees,and the switching of tumor cells from T H2 type to T H0/T H1 may reduce the resistance of tumor cells to NK cytotoxicity markedly.