Zhang Cai, Tian Zhi-gang, Zhang Jian, Feng Jin-bo, Zhang Jian-hua, Xu Xiao-qun
Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Zhonghua Zhong Liu Za Zhi. 2004 Jun;26(6):324-7.
To investigate the regulatory effect of IFN-gamma on recognition of target cells by human natural killer (NK) cells.
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.
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-gamma (> 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.
IFN-gamma 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.
研究γ干扰素对人自然杀伤(NK)细胞识别靶细胞的调节作用。
采用MTT法检测人NK细胞系(NK92、NKL)的细胞毒活性。通过RT-PCR检测靶细胞(NKG2D的配体)上NK细胞受体(NKG2D、NKG2A/B、KIR2DL1和KIR2DS1)及MICA的表达。
NK92和NKL细胞对表达MICA的肿瘤细胞均具有较高的细胞毒性,而不表达MICA的肿瘤细胞可抵抗NK细胞的裂解。γ干扰素(>1000 U/ml)通过下调NKG2D的表达,但上调NKG2A/B和KIR2DL1的表达,抑制NK细胞对表达MICA的肿瘤细胞的裂解。
γ干扰素通过改变NK细胞上激活型和抑制型受体表达之间的平衡,使其偏向抑制,从而对人NK细胞的激活和细胞毒性产生负面影响。这可能有助于限制体内NK细胞的过度激活。