Targeted Activation of Human Vγ9Vδ2-T Cells Controls Epstein-Barr Virus-Induced B Cell Lymphoproliferative Disease

被引：121
|
作者：
Xiang, Zheng [1 ]
Liu, Yinping [1 ]
Zheng, Jian [1 ]
Liu, Ming [2 ]
Lv, Aizhen [1 ]
Gao, Yulong [1 ]
Hu, Huaidong [3 ]
Lam, Kowk-Tai [1 ]
Chan, Godfrey Chi-Fung [1 ]
Yang, Yuanzhong [4 ]
Chen, Honglin [5 ]
Tsao, George Sai-Wah [6 ]
Bonneville, Marc [7 ,8 ]
Lau, Yu-Lung [1 ]
Tu, Wenwei [1 ]
机构：
[1] Univ Hong Kong, Li Ka Shing Fac Med, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China
[2] Guangzhou Med Univ, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China
[3] Chongqing Med Univ, Affiliated Hosp 2, Minist Educ, Key Lab Mol Biol Infect Dis, Chongqing, Peoples R China
[4] Sun Yat Sen Univ, Ctr Canc, Dept Pathol, Guangzhou 510275, Guangdong, Peoples R China
[5] Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China
[6] Univ Hong Kong, Li Ka Shing Fac Med, Dept Anat, Hong Kong, Hong Kong, Peoples R China
[7] Univ Nantes, Ctr Rech Cancerol Nantes Angers, F-44300 Nantes, France
[8] INSERM U892 CNRS UMR6299, F-44300 Nantes, France
来源：
CANCER CELL | 2014年 / 26卷 / 04期
关键词：
DELTA-T-CELLS; GAMMA-DELTA; EBV INFECTION; LYMPHOCYTES; EXPRESSION; MICE; PHOSPHOANTIGEN; IMMUNOTHERAPY; CYTOTOXICITY; STIMULATION;
D O I：
10.1016/j.ccr.2014.07.026
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
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 V gamma 9V delta 2-T cells efficiently killed EBV-transformed autologous lymphoblastoid B cell lines (EBV-LCL) through gamma/delta-TCR and NKG2D receptor triggering and Fas and TRAIL engagement. By inoculation of EBV-LCL in Rag2(-/-)gamma C-/- mice and humanized mice, we established lethal EBV-LPD with characteristics close to those of the human disease. Adoptive transfer of pamidronate-expanded V gamma 9V delta 2-T cells alone effectively prevented EBV-LPD in Rag2(-/-)gamma C-/- mice and induced EBV-LPD regression in EBV+ tumor-bearing Rag2-/-yc-/- mice. Pamidronate treatment inhibited EBV-LPD development in humanized mice through selective activation and expansion of V gamma 9V delta 2-T cells. This study provides proof-of-principle for a therapeutic approach using pamidronate to control EBV-LPD through V gamma 9V delta 2-T cell targeting.
引用
收藏
页码：565 / 576
页数：12
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