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

Abstract

Vγ9/Vδ2 (γδ) 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 γδ T cells and regulate immune responses mediated by conventional αβ 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. Zoltreated iDC and mDC retained their immunostimulatory properties and induced the vigorous expansion of central memory and effector memory γδ T cells. γδ 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 αβ T cells, were improved by the concurrent γβ T-cell activation. In conclusion, large numbers of γβ 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. © 2007 by The American Society of Hematology.