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Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes
Background: Human Vγ9Vδ2 γδ T cells can kill a variety of cancer cells and have attracted substantial interest for cancer immunotherapy. Toll-like receptor (TLR) ligands are promising adjuvants for cancer immunotherapy, but TLR7/8 ligand Resiquimod has been shown to inhibit CD4 T-cell activation in...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140608/ https://www.ncbi.nlm.nih.gov/pubmed/32183240 http://dx.doi.org/10.3390/cells9030713 |
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author | Serrano, Ruben Wesch, Daniela Kabelitz, Dieter |
author_facet | Serrano, Ruben Wesch, Daniela Kabelitz, Dieter |
author_sort | Serrano, Ruben |
collection | PubMed |
description | Background: Human Vγ9Vδ2 γδ T cells can kill a variety of cancer cells and have attracted substantial interest for cancer immunotherapy. Toll-like receptor (TLR) ligands are promising adjuvants for cancer immunotherapy, but TLR7/8 ligand Resiquimod has been shown to inhibit CD4 T-cell activation in a monocyte-dependent manner. Therefore, we studied the modulation of human γδ T-cell activation by TLR7/8 ligands. Methods: Peripheral blood mononuclear cells (PBMC) or purified γδ T cells together with purified monocytes were stimulated with zoledronic acid or phosphoantigens in the absence or presence of various imidazoquinoline TLR7 or TLR8 agonists. Read-out systems included interferon-γ induction and cellular expansion of γδ T cells, as well as viability, cell surface antigen modulation, and IL-1β and TNF-α production of monocytes. Results: TLR8 ligand TL8-506 and TLR7/8 ligand Resiquimod (but not TLR7 ligands) rapidly induced IFN-γ expression in γδ T cells within PBMC, and co-stimulated phosphoantigen-induced IFN-γ expression in γδ T cells. On the other hand, TLR8 ligands potently suppressed γδ T-cell expansion in response to zoledronic acid and phosphoantigen. Purified monocytes secreted large amounts of IL-1β and TNF-α when stimulated with TLR8 ligands but simultaneously underwent substantial cell death after 24 h. Conclusions: TLR8 ligand-activated monocytes potently co-stimulate early γδ T-cell activation but failed to provide accessory cell function for in vitro expansion of γδ T cells. |
format | Online Article Text |
id | pubmed-7140608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71406082020-04-13 Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes Serrano, Ruben Wesch, Daniela Kabelitz, Dieter Cells Article Background: Human Vγ9Vδ2 γδ T cells can kill a variety of cancer cells and have attracted substantial interest for cancer immunotherapy. Toll-like receptor (TLR) ligands are promising adjuvants for cancer immunotherapy, but TLR7/8 ligand Resiquimod has been shown to inhibit CD4 T-cell activation in a monocyte-dependent manner. Therefore, we studied the modulation of human γδ T-cell activation by TLR7/8 ligands. Methods: Peripheral blood mononuclear cells (PBMC) or purified γδ T cells together with purified monocytes were stimulated with zoledronic acid or phosphoantigens in the absence or presence of various imidazoquinoline TLR7 or TLR8 agonists. Read-out systems included interferon-γ induction and cellular expansion of γδ T cells, as well as viability, cell surface antigen modulation, and IL-1β and TNF-α production of monocytes. Results: TLR8 ligand TL8-506 and TLR7/8 ligand Resiquimod (but not TLR7 ligands) rapidly induced IFN-γ expression in γδ T cells within PBMC, and co-stimulated phosphoantigen-induced IFN-γ expression in γδ T cells. On the other hand, TLR8 ligands potently suppressed γδ T-cell expansion in response to zoledronic acid and phosphoantigen. Purified monocytes secreted large amounts of IL-1β and TNF-α when stimulated with TLR8 ligands but simultaneously underwent substantial cell death after 24 h. Conclusions: TLR8 ligand-activated monocytes potently co-stimulate early γδ T-cell activation but failed to provide accessory cell function for in vitro expansion of γδ T cells. MDPI 2020-03-13 /pmc/articles/PMC7140608/ /pubmed/32183240 http://dx.doi.org/10.3390/cells9030713 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Serrano, Ruben Wesch, Daniela Kabelitz, Dieter Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes |
title | Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes |
title_full | Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes |
title_fullStr | Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes |
title_full_unstemmed | Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes |
title_short | Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes |
title_sort | activation of human γδ t cells: modulation by toll-like receptor 8 ligands and role of monocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140608/ https://www.ncbi.nlm.nih.gov/pubmed/32183240 http://dx.doi.org/10.3390/cells9030713 |
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