IL-23R and TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells expressing high levels of cytotoxic mediators and producing IFN-γ and IL-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 V gamma 9V delta 2 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 aminobisphos-phonate zoledronate). As increasing evidence indicates that gamma delta T cells are especially important in early life, we investigated the effect of IL-23 on neonatal V gamma 9V delta 2 T cells stimulated via their TCR. Zoledronate induced clear proliferation and IFN-gamma production in neonatal V gamma 9V delta 2 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-gamma and generated a distinct, IFN-gamma-negative, neonatal V gamma 9V delta 2 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-gamma and cytotoxic mediators was also observed within adult V gamma 9V delta 2Z T cells, the induction of an IL-17 + IFN-gamma-subset was unique to neonatal V gamma 9V delta 2 T cells. In conclusion, neonatal DC-derived IL-23 combined with specific TCR signaling drives the generation of neonatal V gamma 9V delta 2 T cells equipped with a range of cytotoxic mediators and distinct subpopulations producing IFN-gamma and IL-17. J. Leukoc. Biol. 89: 743-752; 2011.