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

• DOI: 10.1016/j.ccr.2014.07.026
• Publication Date: 2014-09-11T16:48:47Z
• Authors: Zheng Xiang; Yinping Liu; Jian Zheng; Ming Liu; Aizhen Lv; Yulong Gao; Huaidong Hu; Kowk-Tai Lam; Godfrey Chi-Fung ...; Yuanzhong Yang; Honglin Chen; George Sai-Wah Tsao; Marc Bonneville; Yu-Lung Lau; Wenwei Tu
• Keywords: Lymphoproliferative disease; RAG2; Adoptive Cell Transfer; NKG2D

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.