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Author Notes:

Address correspondence to: Roberto Pacifici, M.D. Division of Endocrinology, Metabolism and Lipids Emory University School of Medicine 101 Woodruff Circle, Room 1309 Atlanta, GA 30322 Telephone: 404-712-8420 Fax: 404-727-1300 roberto.pacifici@emory.edu


Research Funding:

This study was supported by a grant from the National Institutes of Health (AR54625)


  • parathyroid hormone
  • bone loss
  • T cell
  • lymphocyte
  • bone resorption

Inhibition of antigen presentation and T cell costimulation blocks PTH-induced bone loss


Journal Title:

Annals of the New York Academy of Sciences


Volume 1192


, Pages 215-221

Type of Work:

Article | Post-print: After Peer Review


T cells are required for continuous PTH (cPTH) treatment to induce bone loss as they sensitize SCs to PTH through CD40 Ligand (CD40L), a surface molecule of activated T cells. Since CD40L expression is a feature of activated T cells, we investigated whether antigen (Ag) mediated T cell activation is required for PTH to exert its catabolic activity. We report that inhibition of Ag presentation through silencing of either class I or class II MHC-T cell receptor (TCR) interaction prevents the cortical bone loss induced by in vivo cPTH treatment. We also show that the bone loss and the stimulation of bone resorption induced by cPTH treatment are prevented by CTLA4-Ig, an inhibitor of T cell costimulation approved for the treatment of Rheumatoid Arthritis. Since inhibition of antigen driven T cell activation by blockade of either TCR signaling or T cell costimulation is sufficient to silence the catabolic activity of cPTH, antigen presenting cells and T lymphocyte interactions therefore play a critical role in the mechanism of action of PTH.

Copyright information:

© 2010 New York Academy of Sciences

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