In vitro effects of aminobisphosphonates on Vgamma9Vdelta2 T cell activation and differentiation.

In this study we have evaluated the in vitro effects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on Vgamma9Vdelta2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of Vgamma9Vdelta2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of Vgamma9Vdelta2 T cell subsets, with decrease of T(naive) and T(CM) cells and increase of T(EM) and T(EMRA) Vgamma9Vdelta2cells, indicating that in vitro treatment with aminobisphosphonates induces Vgamma9Vdelta2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, Vgamma9Vdelta2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-gamma and acquired the ability to kill tumor target cells.