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