In vitro effects of aminobisphosphonates on Vγ9Vδ2 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 V gamma 9V delta 2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of V gamma V delta 2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of V gamma 9V delta 2 T cell subsets, with decrease of T-naive and T-CM cells and increase of T-EM and T-EMRA V gamma 9V delta 2 cells, indicating that in vitro treatment with ammobisphosphonates induces V gamma 9V delta 2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, V gamma 9V delta 2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-gamma and acquired the ability to kill tumor target cells.