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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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Submitted September 5, 2006
Accepted March 19, 2007
Enhanced ability of dendritic cells to stimulate innate and adaptive immunity upon short-term incubation with zoledronic acid
Francesca Fiore, Barbara Castella, Barbara Nuschak, Raffaello Bertieri, Sara Mariani, Benedetto Bruno, Francesca Pantaleoni, Myriam Foglietta, Mario Boccadoro, and Massimo Massaia*
Divisione di Ematologia dell'Universita di Torino, Centro di Ricerca Medicina Sperimentale (CeRMS), Ospedale San Giovanni Battista, Torino, Italy
Laboratorio di Ematologia Oncologica, Centro di Ricerca Medicina Sperimentale (CeRMS), Ospedale San Giovanni Battista, Torino, Italy
Novartis Farma, Origgio, Italy
* Corresponding author; email: massimo.massaia{at}unito.it.
V 9/V 2 ()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 aminobisphosphonate (ABP)-treated monocytes. The aim of this work was to determine whether ABP-treated dendritic cells (DC) can also activate T cells and regulate immune responses mediated by conventional   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 T cells. 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 T cells, were improved by the concurrent T-cell activation. In conclusion, large numbers of 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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[Abstract]
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