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

Abstract

AbstractVγ9/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. Zol-treated 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 γδ T-cell activation. In conclusion, large numbers of γδ 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.