Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands

Abstract Human Vγ9Vδ2 T cells recognize pyrophosphates produced by microbes and transformed cells and play a role in anti-infective immunity and tumor surveillance. Toll-like receptors (TLR) are pattern recognition receptors in innate immune cells which sense microbial structures including nucleic a...

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Autores principales:	Ruben Serrano, Christoph Coch, Christian Peters, Gunther Hartmann, Daniela Wesch, Dieter Kabelitz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b641f3f4ca8948f881ad01de1b5a59b8
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spelling	oai:doaj.org-article:b641f3f4ca8948f881ad01de1b5a59b82021-12-02T18:47:00ZMonocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands10.1038/s41598-021-94428-62045-2322https://doaj.org/article/b641f3f4ca8948f881ad01de1b5a59b82021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94428-6https://doaj.org/toc/2045-2322Abstract Human Vγ9Vδ2 T cells recognize pyrophosphates produced by microbes and transformed cells and play a role in anti-infective immunity and tumor surveillance. Toll-like receptors (TLR) are pattern recognition receptors in innate immune cells which sense microbial structures including nucleic acids. Given that γδ T cells are in clinical development for application in cellular cancer immunotherapy and TLR ligands have potent adjuvant activity, we investigated the co-stimulatory role of selected TLR ligands in γδ T-cell activation. Here we have used recently described RNA ligands for TLR7 and TLR8 together with Vγ9Vδ2 T-cell specific pyrophosphate antigens to analyze the rapid cytokine induction in Vδ2 T cells as well as the accessory cell requirements. While TLR8- as well as TLR7/8-specific RNA did not induce IFN-γ in Vδ2 T cells on their own, they provided strong co-stimulation for Vδ2 T cells within peripheral blood mononuclear cells in the presence of additional T-cell receptor activation. In contrast, TLR7 ligands were ineffective. Purified γδ T cells did not directly respond to TLR8 co-stimulation but required the presence of monocytes. Further experiments revealed a critical role of IL-1β and IL-18, and to a slightly lesser extent of IL-12p70, in the co-stimulation of Vδ2 T cells by TLR8 and TLR7/8 RNA ligands. Results of intracellular cytokine expression were validated by ELISA analysis of cytokines in cell culture supernatants. The cell context-dependent adjuvant activity of TLR8 and TLR7/8 RNA ligands described here might be important for the future optimization of γδ T-cell based cancer immunotherapy.Ruben SerranoChristoph CochChristian PetersGunther HartmannDaniela WeschDieter KabelitzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ruben Serrano Christoph Coch Christian Peters Gunther Hartmann Daniela Wesch Dieter Kabelitz Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
description	Abstract Human Vγ9Vδ2 T cells recognize pyrophosphates produced by microbes and transformed cells and play a role in anti-infective immunity and tumor surveillance. Toll-like receptors (TLR) are pattern recognition receptors in innate immune cells which sense microbial structures including nucleic acids. Given that γδ T cells are in clinical development for application in cellular cancer immunotherapy and TLR ligands have potent adjuvant activity, we investigated the co-stimulatory role of selected TLR ligands in γδ T-cell activation. Here we have used recently described RNA ligands for TLR7 and TLR8 together with Vγ9Vδ2 T-cell specific pyrophosphate antigens to analyze the rapid cytokine induction in Vδ2 T cells as well as the accessory cell requirements. While TLR8- as well as TLR7/8-specific RNA did not induce IFN-γ in Vδ2 T cells on their own, they provided strong co-stimulation for Vδ2 T cells within peripheral blood mononuclear cells in the presence of additional T-cell receptor activation. In contrast, TLR7 ligands were ineffective. Purified γδ T cells did not directly respond to TLR8 co-stimulation but required the presence of monocytes. Further experiments revealed a critical role of IL-1β and IL-18, and to a slightly lesser extent of IL-12p70, in the co-stimulation of Vδ2 T cells by TLR8 and TLR7/8 RNA ligands. Results of intracellular cytokine expression were validated by ELISA analysis of cytokines in cell culture supernatants. The cell context-dependent adjuvant activity of TLR8 and TLR7/8 RNA ligands described here might be important for the future optimization of γδ T-cell based cancer immunotherapy.
format	article
author	Ruben Serrano Christoph Coch Christian Peters Gunther Hartmann Daniela Wesch Dieter Kabelitz
author_facet	Ruben Serrano Christoph Coch Christian Peters Gunther Hartmann Daniela Wesch Dieter Kabelitz
author_sort	Ruben Serrano
title	Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
title_short	Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
title_full	Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
title_fullStr	Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
title_full_unstemmed	Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
title_sort	monocyte-dependent co-stimulation of cytokine induction in human γδ t cells by tlr8 rna ligands
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b641f3f4ca8948f881ad01de1b5a59b8
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Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands

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