Zoledronic acid renders human M1 and M2 macrophages susceptible to Vδ2+ γδ T cell cytotoxicity in a perforin-dependent manner

Cancer Immunology, Immunotherapy : CII
Daniel W FowlerMark D Bodman-Smith

Abstract

Vδ2+ T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2+ T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. In this study we focussed on macrophages (Mϕs), as these cells have been shown to take up ZA. We differentiated peripheral blood monocytes from healthy donors into Mϕs and then treated them with IFN-γ or IL-4 to generate M1 and M2 Mϕs, respectively. We characterised these Mϕs based on their phenotype and cytokine production and then tested whether ZA rendered them susceptible to Vδ2+ T cell cytotoxicity. Consistent with the literature, IFN-γ-treated Mϕs expressed higher levels of the M1 markers CD64 and IL-12p70, whereas IL-4-treated Mϕs expressed higher levels of the M2 markers CD206 and chemokine (C-C motif) ligand 18. When treated with ZA, both M1 and M2 Mϕs became susceptible to Vδ2+ T cell cytotoxicity. Vδ2+ T cells expressed perforin and degranulated in response to ZA-treated Mϕs as shown by mobilisatio...Continue Reading

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Citations

Jan 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Weiwen ZhuHongbing Jiang
Oct 14, 2019·Immunology·Loïc RaffrayMatthias Eberl
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Apr 20, 2018·Frontiers in Immunology·David A RhodesMatthias Eberl
Sep 3, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yu-Chun ChangChristopher Breuer

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Methods Mentioned

BETA
light microscopy
flow cytometry
ELISA
ELISAs

Software Mentioned

Genstat
GraphPad Prism
FlowJo

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