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肿瘤坏死因子-α相关凋亡诱导配体参与脂多糖刺激的树突状细胞对活化T细胞细胞毒性增强的过程。

Involvement of tumour necrosis factor-alpha-related apoptosis-inducing ligand in enhanced cytotoxicity of lipopolysaccharide-stimulated dendritic cells to activated T cells.

作者信息

Yu Yizhi, Liu Shuxun, Wang Wenya, Song Wengang, Zhang Minghui, Zhang Weiping, Qin Zhihai, Cao Xuetao

机构信息

Institute of Immunology, Second Military Medical University, Shanghai People's Republic of China.

出版信息

Immunology. 2002 Jul;106(3):308-15. doi: 10.1046/j.1365-2567.2002.01431.x.

Abstract

Dendritic cells (DC) are potent antigen-presenting cells (APC) specialized in T-cell mediated immune responses, and also play critical roles in the homeostasis of T cells for controlling immune responses. In the present study, we demonstrated that during mouse bone-marrow-derived DC activation of ovalbumin (OVA)-specific Ia-kb-restricted T hybridoma cells, MF2.2D9 and OVA257-264-specific H-2kb-restricted RF33.70 T cells, respectively, both hybridomas undergo cell death, partially mediated via apoptotic ligand-tumour necrosis factor-alpha (TNF-alpha)-related apoptosis-inducing ligand (TRAIL). Lipopolysaccharide enhanced the cytotoxic effect on the two activated T hybridoma cells, which was correlated with up-regulation of TRAIL-expression on DC to some extent. The activation of caspase-3 in activated T hybridoma cells cocultured with DC contributed to the programmed cell death pathway T cells underwent. Therefore, our results show that activation-induced cell death of T hybridoma cells can be influenced by DC, suggesting that DC may be involved in elimination of activated T cells at the end of primary immune responses.

摘要

树突状细胞(DC)是强大的抗原呈递细胞(APC),专门参与T细胞介导的免疫反应,并且在T细胞稳态以控制免疫反应中也发挥关键作用。在本研究中,我们证明,在小鼠骨髓来源的DC激活卵清蛋白(OVA)特异性的Ia-kb限制性T杂交瘤细胞、MF2.2D9以及OVA257-264特异性的H-2kb限制性RF33.70 T细胞的过程中,两种杂交瘤细胞均发生细胞死亡,部分是通过凋亡配体——肿瘤坏死因子-α(TNF-α)相关凋亡诱导配体(TRAIL)介导的。脂多糖增强了对两种活化T杂交瘤细胞的细胞毒性作用,这在一定程度上与DC上TRAIL表达上调相关。与DC共培养的活化T杂交瘤细胞中caspase-3的激活促成了T细胞所经历的程序性细胞死亡途径。因此,我们的结果表明,T杂交瘤细胞的激活诱导细胞死亡可受DC影响,提示DC可能参与初次免疫反应末期活化T细胞的清除。

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