摘要
目的 探讨γ干扰素 (IFN γ)对人NK细胞识别功能的负调节作用。方法 用MTT法测定人NK细胞系 (NK92 ,NKL)的细胞毒活性及细胞增殖能力 ;用RT PCR检测NK细胞受体 (NKG2D、NKG2A/B、KIR2DL1、KIR2DS1)及NKG2D的识别配体主要组织相容性复合体Ⅰ类链相关分子A(MICA)的表达。结果 NK细胞系 (NK92、NKL)对MICA表达阳性的肿瘤细胞杀伤活性明显高于对MICA表达阴性者 ;IFN γ 10 0 0U/ml以上可明显抑制NK细胞对MICA表达阳性肿瘤细胞的细胞毒活性 ,并轻度抑制NK细胞的增殖 ,而对MICA表达阴性肿瘤细胞的杀伤活性无明显抑制作用 ;IFN γ可抑制NK细胞系活化受体NKG2D的表达 ,增强抑制性受体NKG2A/B和KIR2DL1的表达。结论 IFN γ可能通过下调NK细胞活化受体的表达 ,上调抑制性受体的表达 ,使NK识别的信号平衡向抑制性方向倾斜 ,从而对NK细胞功能发挥负调节作用 。
Objective To investigate the regulatory effect of IFN γ on recognition of target cells by human natural killer (NK) cells. Methods The cytotoxic activity of human NK cell lines (NK92, NKL) was detected by MTT method. Expression of NK cell receptors ( NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA on target cells (the ligand of NKG2D) was measured by RT PCR. Results Both NK92 and NKL cells exerted higher cytotoxicity to tumor cells with MICA expression, while tumors without MICA expression could resist NK cell lysis. IFN γ (>1000 U/ml) inhibited NK lysis of tumor cells with MICA expression through down regulating the expression of NKG2D, but up regulating the expression of NKG2A/B and KIR2DL1. Conclusion IFN γ has a negative effect on activation and cytotoxicity of human NK cells by altering the balance between the expression of activating and inhibitory receptors on NK cells in favor of inhibition. This may serve to limit NK cell over activation in vivo.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2004年第6期324-327,共4页
Chinese Journal of Oncology
基金
国家自然科学基金重点资助项目(3 0 2 3 0 3 40 )
国家自然科学基金资助项目(3 0 3 713 0 2)
国家863资助项目 (2 0 0 2AA2 1615 1)
国家973资助项目(2 0 0 1CB5 10 0 0 9)
国家杰出青年基金资助项目(3 0 12 5 0 3 8)
国家知识创新工程资助项目(KSCX2 2 0 8)
