Next Article in Journal
Ets Family Transcription Factor Fli-1 Promotes Leukocyte Recruitment and Production of IL-17A in the MRL/Lpr Mouse Model of Lupus Nephritis
Next Article in Special Issue
Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature
Previous Article in Journal
Mitochondria in the Nuclei of Rat Myocardial Cells
Previous Article in Special Issue
The Role of Tissue-resident γδ T Cells in Stress Surveillance and Tissue Maintenance
Open AccessArticle

Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes

Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 713; https://doi.org/10.3390/cells9030713
Received: 16 February 2020 / Revised: 10 March 2020 / Accepted: 11 March 2020 / Published: 13 March 2020
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. View Full-Text
Keywords: gamma delta T cells; inflammasome; monocytes; phosphoantigen; Resiquimod; Toll-like receptors; zoledronic acid gamma delta T cells; inflammasome; monocytes; phosphoantigen; Resiquimod; Toll-like receptors; zoledronic acid
Show Figures

Figure 1

MDPI and ACS Style

Serrano, R.; Wesch, D.; Kabelitz, D. Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes. Cells 2020, 9, 713.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop