Cargando…
Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
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. Giv...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316369/ https://www.ncbi.nlm.nih.gov/pubmed/34315922 http://dx.doi.org/10.1038/s41598-021-94428-6 |
_version_ | 1783729845389230080 |
---|---|
author | Serrano, Ruben Coch, Christoph Peters, Christian Hartmann, Gunther Wesch, Daniela Kabelitz, Dieter |
author_facet | Serrano, Ruben Coch, Christoph Peters, Christian Hartmann, Gunther Wesch, Daniela Kabelitz, Dieter |
author_sort | Serrano, Ruben |
collection | PubMed |
description | 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 | Online Article Text |
id | pubmed-8316369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83163692021-07-28 Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands Serrano, Ruben Coch, Christoph Peters, Christian Hartmann, Gunther Wesch, Daniela Kabelitz, Dieter Sci Rep Article 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. Nature Publishing Group UK 2021-07-27 /pmc/articles/PMC8316369/ /pubmed/34315922 http://dx.doi.org/10.1038/s41598-021-94428-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Serrano, Ruben Coch, Christoph Peters, Christian Hartmann, Gunther Wesch, Daniela Kabelitz, Dieter Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316369/ https://www.ncbi.nlm.nih.gov/pubmed/34315922 http://dx.doi.org/10.1038/s41598-021-94428-6 |
work_keys_str_mv | AT serranoruben monocytedependentcostimulationofcytokineinductioninhumangdtcellsbytlr8rnaligands AT cochchristoph monocytedependentcostimulationofcytokineinductioninhumangdtcellsbytlr8rnaligands AT peterschristian monocytedependentcostimulationofcytokineinductioninhumangdtcellsbytlr8rnaligands AT hartmanngunther monocytedependentcostimulationofcytokineinductioninhumangdtcellsbytlr8rnaligands AT weschdaniela monocytedependentcostimulationofcytokineinductioninhumangdtcellsbytlr8rnaligands AT kabelitzdieter monocytedependentcostimulationofcytokineinductioninhumangdtcellsbytlr8rnaligands |