RESUMO
No disponible
Assuntos
Humanos , Masculino , Feminino , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/complicações , Dermatite Atópica/imunologia , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/complicações , Linfócitos T , Linfócitos T/imunologia , Alendronato/efeitos adversos , Alendronato/imunologia , Quimiocinas/análise , Quimiocinas/imunologia , Biomarcadores/análiseRESUMO
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 gammadelta T cells in vitro and in vivo (potency: risedronate > alendronate > pamidronate) requires expression of the Vgamma2Vdelta2 TCR and is thus Vgamma2Vdelta2 TCR-dependent. Myeloma cells or monocytes pulsed with risedronate and then washed rendered these target cells sensitive to lysis by a Vgamma2Vdelta2 T-cell clone or cell line. These results suggest that Vgamma2Vdelta2 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.
