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Peripheral blood monocytes are responsible for γδ T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP
Article first published online: 11 NOV 2008
© 2008 The Authors. Journal Compilation © 2008 Blackwell Publishing Ltd
British Journal of Haematology
Volume 144, Issue 2, pages 245–250, January 2009
How to Cite
Roelofs, A. J., Jauhiainen, M., Mönkkönen, H., Rogers, M. J., Mönkkönen, J. and Thompson, K. (2009), Peripheral blood monocytes are responsible for γδ T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP. British Journal of Haematology, 144: 245–250. doi: 10.1111/j.1365-2141.2008.07435.x
- Issue published online: 17 DEC 2008
- Article first published online: 11 NOV 2008
- Received 1 June 2008; accepted for publication 26 August 2008
- gamma delta T cells;
- isopentenyl diphosphate
Nitrogen-containing bisphosphonates indirectly activate Vγ9Vδ2 T cells through inhibition of farnesyl pyrophosphate synthase and intracellular accumulation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), but the cells responsible for Vγ9Vδ2 T cell activation through IPP/DMAPP accumulation are unknown. Treatment of human peripheral blood mononuclear cells (PBMCs) with a pharmacologically relevant concentration of zoledronic acid induced accumulation of IPP/DMAPP selectively in monocytes, which correlated with efficient drug uptake by these cells. Furthermore, zoledronic acid-pulsed monocytes triggered activation of γδ T cells in a cell contact-dependent manner. These observations identify monocytes as the cell type directly affected by bisphosphonates responsible for Vγ9Vδ2 T cell activation.