摘要
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 γδ2-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus.
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 γδ2-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus.
基金
This work was supported in part by the National Natural Science Foundation of China （No. 30973235）, Science and Technology Project of the Sichuan Science and Technology Department （2010SZ0110）, General Research Fund, Research Grants Council of Hung Kong （HKU 781211M） and the Area of Excellence Scheme of the University Grants Committee, Hung Kong SAR, China （AoE/M-12/06）.
