title: Targeted activation of human Vγ9Vδ2-T cells controls epstein-barr virus-induced B cell lymphoproliferative disease.
abstract: 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.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Yinping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Guangzhou Institute of Respiratory Diseases, Guangzhou Medical College, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Lv
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Kowk-Tai
authors.initials: KT
authors.lastname: Lam
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Godfrey Chi-Fung
authors.initials: GC
authors.lastname: Chan
authors.affiliation: Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: George Sai-Wah
authors.initials: GS
authors.lastname: Tsao
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, Université de Nantes, 44300 Nantes, France; INSERM U892 CNRS UMR6299, 44300 Nantes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneville
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. Electronic address: wwtu@hku.hk.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000503:physiopathology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*