Dataset Information

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

ABSTRACT: BACKGROUND:Human V?9V?2 ?? 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 ?? T-cell activation by TLR7/8 ligands. METHODS:Peripheral blood mononuclear cells (PBMC) or purified ?? 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-? induction and cellular expansion of ?? T cells, as well as viability, cell surface antigen modulation, and IL-1? and TNF-? production of monocytes. RESULTS:TLR8 ligand TL8-506 and TLR7/8 ligand Resiquimod (but not TLR7 ligands) rapidly induced IFN-? expression in ?? T cells within PBMC, and co-stimulated phosphoantigen-induced IFN-? expression in ?? T cells. On the other hand, TLR8 ligands potently suppressed ?? T-cell expansion in response to zoledronic acid and phosphoantigen. Purified monocytes secreted large amounts of IL-1? and TNF-? when stimulated with TLR8 ligands but simultaneously underwent substantial cell death after 24 h. CONCLUSIONS:TLR8 ligand-activated monocytes potently co-stimulate early ?? T-cell activation but failed to provide accessory cell function for in vitro expansion of ?? T cells.

SUBMITTER: Serrano R

PROVIDER: S-EPMC7140608 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Serrano Ruben R Wesch Daniela D Kabelitz Dieter D

Cells 20200313 3

<h4>Background</h4>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.<h4>Methods</h4>Peripheral blood mononuclear cells (PBMC) or purified γδ T cell ...[more]

PMID: 32183240

Similar Datasets

Project description:Eosinophils are terminally differentiated granulocytes that have long been considered as destructive cells associated with Th2 type immune responses such as allergic inflammation and helminth infections. Recently, eosinophils have been actively studied as multifunctional leukocytes regulating an array of physiological responses through interaction with other immune cells. In this study, we examined the expression and function of Toll-like receptors (TLRs) in eosinophilic EoL-1 cells and demonstrated the expression of a number of immune mediators in activated EoL-1 cells and their interaction with the macrophage cell line THP-1 upon TLR4 ligand stimulation. EoL-1 cells differentiated with butyrate increased expression of TLR3, TLR4, and TLR7 at mRNA and protein level with flow cytometry analysis. Mature eosinophils derived from human cord blood CD34+ cells were subjected to RNA-sequencing, and showed the expression of a panel of TLR transcripts and TLR4 was the most highly expressed TLR. Among the cognate ligands of TLR3, TLR4, and TLR7, lipopolysaccharide (LPS) or palmitic acid significantly increased mRNA expression of immune mediators in differentiated EoL-1 cells. Notably, Western blot analysis of palmitic acid-treated differentiated EoL-1 cells showed significantly up-regulated expression of Th2 type cytokines and transcription factors driving eosinophil differentiation. To evaluate functional significance of TLR4 ligand-stimulated eosinophils, we added conditioned media (CM) from EoL-1 cells to differentiated THP-1 cells and assessed the expression of M1 macrophage or M2 macrophage-related markers. M1 and M2 macrophage markers were significantly upregulated by CM from LPS and palmitic acid stimulated EoL-1 cells, respectively. In addition, the adipose tissue of obese mice, where eosinophils are decreased due to obesity-induced inflammation, showed significantly decreased frequency of M2 macrophages, despite an increase in the total macrophage numbers. Based on these collective data, we proposed that eosinophils regulate both inflammatory and anti-inflammatory polarization of macrophages through functional changes induced by different TLR4 ligands.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets