V gamma 2V delta 2 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 metasta ses that are characterized by excessive osteoclastic bone resorption. Using T-cell receptor (TCR) transfer studies, we show that recognition of antige nic aminobisphosphonates that are known to stimulate human gamma delta T ce lls In vitro and In vivo (potency: risedronate > alendronate > pamidronate) requires expression of the V gamma 2V delta2 TCR and is thus V gamma 2V de lta2 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 del ta2 TCR-dependent recognition leading to direct cytolysis of aminobisphosph onate-sensitized osteoclast or tumor targets may be a mechanism whereby ami nobisphosphonate treatment of cancers metastatic to bone decreases osteocla stic activity and tumor burden and also may account for the decreased osteo clastic activity associated with successful treatment of osteoporosis. (C) 2001 by The American Society of Hematology.