title: 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.
abstract: 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.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Moens
authors.forename: Margreet
authors.initials: M
authors.lastname: Brouwer
authors.forename: Tanya
authors.initials: T
authors.lastname: Dimova
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Fabienne
authors.initials: F
authors.lastname: Willems
authors.forename: David
authors.initials: D
authors.lastname: Vermijlen
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology; D005434:Flow Cytometry; D019672:Genes, T-Cell Receptor / Q000502:physiology*; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D054353:Perforin / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D000077211:Zoledronic Acid
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D004164:Diphosphonates; C075005:GNLY protein, human; C515500:IL23R protein, human; D007093:Imidazoles; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human; D054353:Perforin; D000077211:Zoledronic Acid; D007371:Interferon-gamma; D053804:Granzymes