Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells

Cell Mol Immunol. 2013 Mar;10(2):159-64. doi: 10.1038/cmi.2012.70. Epub 2013 Jan 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Death / immunology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Line, Tumor
  • Cells, Cultured
  • Diphosphonates / pharmacology
  • Dogs
  • Epithelial Cells / immunology*
  • Epithelial Cells / pathology
  • Epithelial Cells / virology*
  • Humans
  • Influenza A virus / immunology*
  • Pamidronate
  • Pulmonary Alveoli / immunology*
  • Pulmonary Alveoli / pathology
  • Pulmonary Alveoli / virology*
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*

Substances

  • Diphosphonates
  • Receptors, Antigen, T-Cell, gamma-delta
  • Pamidronate