Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells.
γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their underlying mechanisms. We found that PAM could selectively activate and expand human Vγ9Vδ2-T cells. PAM-expanded human Vγ9Vδ2-T cells efficiently killed influenza virus-infected lung alveolar epithelial cells and inhibited virus replication. The cytotoxic activity of PAM-expanded Vγ9Vδ2-T cells was dependent on cell-to-cell contact and required NKG2D activation. Perforin-granzyme B, tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas-Fas ligand (FasL) pathways were involved in their cytotoxicity. Our study suggests that targeting γδ-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus.
Joint Research Center of West China Second University Hospital of Sichuan University and Department of Paediatrics and Adolescent Medicine of University of Hong Kong, Sichuan University, Chengdu 610041, China. lh3985@gmail.com
Hong
H
Li
Zheng
Z
Xiang
Ting
T
Feng
Jinrong
J
Li
Yinping
Y
Liu
Yingying
Y
Fan
Qiao
Q
Lu
Zhongwei
Z
Yin
Meixing
M
Yu
Chongyang
C
Shen
Wenwei
W
Tu
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D000077268:Pamidronate; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077268:Pamidronate