Tuesday February 9, 2010, from 12.00 to 13.00
"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 dendritic cells (DC). Human adult Vγ9Vδ2-T cells can be specifically stimulated via their TCR by phosphoantigens (like the pathogen-derived (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate, HMB-PP) or agents and infections that lead to their endogenous accumulation (like the aminobisphosphonate zoledronate). Since increasing evidence indicate that γδ T cells are important in early life, we investigated the effect of IL-23 on neonatal Vγ9Vδ2-T cells stimulated via their TCR. Zoledronate, but not HMB-PP, induced clear proliferation and IFN-γ production in neonatal Vγ9Vδ2-T cells. Addition of IL-23 to zoledronate co-stimulated the expression of IFN-γ and generated a distinct IFN-γ-negative neonatal Vγ9Vδ2-T cell population producing IL-17. Furthermore, IL-23 co-stimulated significantly the expression of a range of cytotoxic mediators (perforin, granzymes, granulysin). While the co-stimulatory effect of IL-23 on IFN-γ and cytotoxic mediators was also observed within adult Vγ9Vδ2-T cells, the induction of IL-17 was a unique property of 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.