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Early Triggering of Exclusive IFN- Responses of Human V9V2 T Cells by TLR-Activated Myeloid and Plasmacytoid Dendritic Cells¹

INSERM, U892, Centre de Recherche en Cancérologie Nantes-Angers, Nantes, France

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 V9V2 T cells, a main human 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- production by V9V2 T cells. This subset contributed to a large extent to the overall PBL IFN- 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. V9V2 T cells were similarly activated by plasmacytoid DC upon TLR8/9 activation or Yellow Fever virus infection. Moreover TLR-induced V9V2 IFN- noncytolytic response led to efficient DC polarization into IL-12p70-producing cells. Our results support an adjuvant role played by V9V2 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by institutional grants from Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de la Recherche (ANR no. A05118GS), Association pour la Recherche sur le Cancer (ARC no. 3662 and no. 4953) and from the Commission of the European Union Program: TB-VAC (LSHP-CT-2003–503367) and Cancer Immunotherapy (E06005NP/EEA06004GNP).

² Address correspondence and reprint requests to Emmanuel Scotet or Marc Bonneville, Institut de Recherche Thérapeutique de l’Université de Nantes, Centre de Recherche en Cancérologie Nantes-Angers, INSERM UMR 892, 8 quai Moncousu, BP 70721, Nantes, France. E-mail addresses: Emmanuel.Scotet{at}inserm.fr or bonnevil{at}inserm.fr

³ Abbreviations used in this paper: DC, dendritic cell; iNKT, invariant NKT; BrHPP, bromohydrin pyrophosphate/Phosphostim; YF, yellow fever; iDC, immature DC; ABP, aminobisphophonate; pDC, plasmacytoid DC; moDC, myeloid DC derived from GM-CSF/IL-4-treated monocytes.

⁴ The online version of this article contains supplemental material.