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Early Triggering of Exclusive IFN-γ Responses of Human Vγ9Vδ2 T Cells by TLR-Activated Myeloid and Plasmacytoid Dendritic Cells

Abstract : gd T cells, a major innate-like T cell subset, are thought to play in vivo an important role in innate and adaptive immune responses to various infection agents like parasites, bacteria, or viruses but the mechanisms contributing to this immune process remain ill defined. Owing to their ability to recognize a broad set of microbial molecular patterns, TLRs represent a major innate pathway through which pathogens induce dendritic cells (DC) maturation and acquisition of immunostimulatory functions. In this study, we studied the effects of various TLR ligands on the activation of human Vg9Vd2 T cells, a main human gd PBL subset, which has been recently involved in the licensing of mycobacteria-infected DC. Both TLR3 and TLR4, but not TLR2 ligands, induced a rapid, strong, and exclusive IFN-g production by Vg9Vd2 T cells. This gd subset contributed to a large extent to the overall PBL IFN-g response induced after short-term TLR stimulation of human PBMC. Importantly, this phenomenon primarily depended on type I IFN, but not IL-12, produced by monocytic DC upon TLR engagement. Vg9Vd2 T cells were similarly activated by plasmacytoid DC upon TLR8/9 activation or Yellow Fever virus infection. Moreover TLR-induced Vg9Vd2 IFN-g noncytolytic response led to efficient DC polarization into IL-12p70-producing cells. Our results support an adjuvant role played by Vg9Vd2 T cells along microbial infections through a particular cross-talk with pathogen-associated molecular patterns-activated DC. Moreover they provide new insights into the mechanisms underlying functional activation of this unique peripheral innate-like T cell subset during viral infections.
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https://www.hal.inserm.fr/inserm-02437109
Contributor : Emmanuel Scotet <>
Submitted on : Monday, January 13, 2020 - 3:26:18 PM
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Marie-Claire Devilder, Sophie Allain, Christelle Dousset, Marc Bonneville, Emmanuel Scotet. Early Triggering of Exclusive IFN-γ Responses of Human Vγ9Vδ2 T Cells by TLR-Activated Myeloid and Plasmacytoid Dendritic Cells. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, ⟨10.4049/jimmunol.0901571⟩. ⟨inserm-02437109⟩

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