IL-23R and TCR signaling drives the generation of neonatal Vgamma9Vdelta2 T cells expressing high levels of cytotoxic mediators and producing IFN-gamma and IL-17

J Leukoc Biol. 2011 May;89(5):743-52. doi: 10.1189/jlb.0910501. Epub 2011 Feb 17.


The immune system in early life is regarded as immature. However, the IL-12 family member IL-23 is highly produced upon TLR stimulation by neonatal DCs. Human adult Vγ9Vδ2 T cells can be stimulated specifically via their TCR by phosphoantigens (as the pathogen-derived HMB-PP) or agents and infections that lead to their endogenous accumulation (as the aminobisphosphonate zoledronate). As increasing evidence indicates that γδ T cells are especially important in early life, we investigated the effect of IL-23 on neonatal Vγ9Vδ2 T cells stimulated via their TCR. Zoledronate induced clear proliferation and IFN-γ production in neonatal Vγ9Vδ2 T cells. In contrast, HMB-PP did not elicit a distinct response unless at high concentrations. Addition of IL-23 to zoledronate enhanced the expression of IFN-γ and generated a distinct, IFN-γ-negative, neonatal Vγ9Vδ2 T cell population producing IL-17. Furthermore, IL-23 significantly enhanced the expression of a range of cytotoxic mediators (perforin, granzymes, granulysin). Although the costimulatory effect of IL-23 on IFN-γ and cytotoxic mediators was also observed within adult Vγ9Vδ2 T cells, the induction of an IL-17+IFN-γ- subset was unique to neonatal Vγ9Vδ2 T cells. In conclusion, neonatal DC-derived IL-23 combined with specific TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells equipped with a range of cytotoxic mediators and distinct subpopulations producing IFN-γ and IL-17.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Diphosphonates / pharmacology
  • Flow Cytometry
  • Genes, T-Cell Receptor / physiology*
  • Granzymes / metabolism
  • Humans
  • Imidazoles / pharmacology
  • Infant, Newborn
  • Interferon-gamma / metabolism*
  • Interleukin-17 / metabolism*
  • Perforin / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Receptors, Interleukin / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / metabolism*
  • Zoledronic Acid


  • Antigens, Differentiation, T-Lymphocyte
  • Diphosphonates
  • GNLY protein, human
  • IL23R protein, human
  • Imidazoles
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin
  • T-cell receptor Vdelta2, human
  • T-cell receptor Vgamma9, human
  • Perforin
  • Zoledronic Acid
  • Interferon-gamma
  • Granzymes