Cytokines enhance human Vγ9Vδ2 T-cell TCR-dependent and TCR-independent effector functions

Kirsty R. Field, Kathleen M. Wragg, Wen Shi Lee, Marc Rigau, Adam P. Uldrich, Stephen J. Kent, Jennifer A. Juno

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Vγ9Vδ2 T cells can recognize various molecules associated with cellular stress or transformation, providing a unique avenue for the treatment of cancers or infectious diseases. Nonetheless, Vγ9Vδ2 T-cell-based immunotherapies frequently achieve suboptimal efficacies in vivo. Enhancing the cytotoxic effector function of Vγ9Vδ2 T cells is one potential avenue through which the immunotherapeutic potential of this subset may be improved. We compared the use of four pro-inflammatory cytokines on the effector phenotype and functions of in vitro expanded Vγ9Vδ2 T cells, and demonstrated TCR-independent cytotoxicity mediated through CD26, CD16, and NKG2D, which could be further enhanced by IL-23, IL-18, and IL-15 stimulation throughout expansion. This work defines promising culture conditions that could improve Vγ9Vδ2 T-cell-based immunotherapies and furthers our understanding of how this subset might recognize and target transformed or infected cells.

Original languageEnglish
Article number2250220
Number of pages12
JournalEuropean Journal of Immunology
Issue number6
Publication statusPublished - Jun 2023


  • cellular activation
  • human γδ T cells
  • pro-inflammatory cytokines
  • TCR-independent cytotoxicity
  • Vγ9Vδ2 T cells

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