In VitroEffects of Aminobisphosphonates on Vγ9Vδ2 T Cell Activation and Differentiation

In this study we have evaluated the in vitroeffects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on Vγ9Vδ2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of Vγ9Vδ2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of Vγ9Vδ2 T cell subsets, with decrease of Tnaiveand TCMcells and increase of TEMand TEMRAVγ9Vδ2 cells, indicating that in vitrotreatment with aminobisphosphonates induces Vγ9Vδ2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, Vγ9Vδ2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-γ and acquired the ability to kill tumor target cells.