Vγ2Vδ2 T-cell receptor-mediated recognition of aminobisphosphonates

Aminobisphosphonates, potent derivatives of bisphosphonates, are frequently used for the treatment of conditions such as osteoporosis and bone metastases that are characterized by excessive osteoclastic bone resorption. Using T-cell receptor (TCR) transfer studies, we show that recognition of antigenic aminobisphosphonates that are known to stimulate human gamma delta T cells In vitro and In vivo (potency: risedronate > alendronate > pamidronate) requires expression of the V gamma 2V delta2 TCR and is thus V gamma 2V delta2 TCR-dependent. Myeloma cells or monocytes pulsed with risedronate and then washed rendered these target cells sensitive to lysis by a V gamma 2V delta2 T-cell clone or cell line. These results suggest that V gamma 2V delta2 TCR-dependent recognition leading to direct cytolysis of aminobisphosphonate-sensitized osteoclast or tumor targets may be a mechanism whereby aminobisphosphonate treatment of cancers metastatic to bone decreases osteoclastic activity and tumor burden and also may account for the decreased osteoclastic activity associated with successful treatment of osteoporosis. (C) 2001 by The American Society of Hematology.