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 Blood, 1 August 2007, Vol. 110, No. 3, pp. 921-927.
Prepublished online as a Blood First Edition Paper on April 2, 2007; DOI 10.1182/blood-2006-09-044321.

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IMMUNOBIOLOGY

Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid

Francesca Fiore1,2, Barbara Castella2, Barbara Nuschak2, Raffaello Bertieri3, Sara Mariani2, Benedetto Bruno1, Francesca Pantaleoni2, Myriam Foglietta1, Mario Boccadoro1, and Massimo Massaia1,2

1 Divisione di Ematologia dell'Università di Torino, Torino, Italy; 2 Laboratorio di Ematologia Oncologica, Centro di Ricerca Medicina Sperimentale (CeRMS), Ospedale San Giovanni Battista, Torino, Italy; 3 Novartis Farma, Origgio, Italy

V{gamma}9/V{delta}2 ({gamma}{delta}) T cells play a major role in innate immunity against microbes, stressed, and tumor cells. They represent less than 5% of peripheral blood lymphocytes but can be activated and expanded in vitro by aminobisphosphonates (ABP)–treated monocytes. The aim of this work was to determine whether ABP-treated dendritic cells (DCs) can also activate {gamma}{delta} T cells and regulate immune responses mediated by conventional {alpha}ß T cells. Highly purified immature (iDC) and mature DC (mDC) were generated from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol-treated iDC and mDC retained their immunostimulatory properties and induced the vigorous expansion of central memory and effector memory {gamma}{delta} T cells. {gamma}{delta} T cells displayed antitumor activity and appropriate cell surface antigens to target secondary lymphoid organs and exert costimulatory activity. Antigen-specific MHC-restricted immune responses, mediated by conventional {alpha}ß T cells, were improved by the concurrent {gamma}{delta} T-cell activation. In conclusion, large numbers of {gamma}{delta} T cells with effector and costimulatory activities are rapidly generated by Zol-treated iDC/mDC. This strategy is worthy of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.


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