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首页> 外文期刊>Cancer Cell >Targeted activation of human vγ9vδ2-T cells controls epstein-barr virus-induced B cell lymphoproliferative disease
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Targeted activation of human vγ9vδ2-T cells controls epstein-barr virus-induced B cell lymphoproliferative disease

机译:人类vγ9vδ2-T细胞的靶向激活控制爱泼斯坦-巴尔病毒诱导的B细胞淋巴增生性疾病

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摘要

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) after transplantation remains a serious and life-threatening complication. Herein we showed that the aminobisphosphonate pamidronate-expanded human Vγ9Vδ2-T cells efficiently killed EBV-transformed autologous lymphoblastoid B cell lines (EBV-LCL) through γ/δ-TCR and NKG2D receptor triggering and Fas and TRAIL engagement. By inoculation of EBV-LCL in Rag2-/-γc-/- mice and humanized mice, we established lethal EBV-LPD with characteristics close to those of the human disease. Adoptive transfer of pamidronate-expanded Vγ9Vδ2-T cells alone effectively prevented EBV-LPD in Rag2-/-γc-/- mice and induced EBV-LPD regression in EBV+ tumor-bearing Rag2-/-γc-/- mice. Pamidronate treatment inhibited EBV-LPD development in humanized mice through selective activation and expansion of Vγ9Vδ2-T cells. This study provides proof-of-principle for a therapeutic approach using pamidronate to control EBV-LPD through Vγ9Vδ2-T cell targeting.
机译:移植后爱泼斯坦-巴尔病毒诱发的淋巴增生性疾病(EBV-LPD)仍然是严重且威胁生命的并发症。在本文中,我们显示了氨基双膦酸盐帕米膦酸盐扩增的人Vγ9Vδ2-T细胞通过γ/δ-TCR和NKG2D受体触发以及Fas和TRAIL参与有效杀死了EBV转化的自体淋巴母细胞B细胞系(EBV-LCL)。通过在Rag2-/-γc-/-小鼠和人源化小鼠中接种EBV-LCL,我们建立了具有与人类疾病相似特征的致死性EBV-LPD。单独接受帕米膦酸酯扩增的Vγ9Vδ2-T细胞有效地预防Rag2-/-γc-/-小鼠中的EBV-LPD,并诱导EBV +荷瘤Rag2-/-γc-/-小鼠中的EBV-LPD退化。帕米膦酸治疗通过选择性激活和扩增Vγ9Vδ2-T细胞而抑制人源化小鼠中EBV-LPD的发育。这项研究为使用帕米膦酸通过Vγ9Vδ2-T细胞靶向控制EBV-LPD的治疗方法提供了原理证明。

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