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

• Type of Material: Article
• Authors: Brahmchetna Bedi, Emory University; Jau-Yi Li, Emory University; Hesham Tawfeek, Emory University; M Neale Weitzmann, Emory University; Roberto Pacifici, Emory University
• Language: English
• Date: 2010-03
• Publisher: New York Academy of Sciences
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 New York Academy of Sciences
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2009.05216.x/abstract
• Title of Journal or Parent Work: Annals of the New York Academy of Sciences
• ISSN: 0077-8923
• Volume: 1192
• Start Page: 215
• End Page: 221
• Grant/Funding Information: This study was supported by a grant from the National Institutes of Health (AR54625)
• Keywords: parathyroid hormone; T cell; bone resorption; lymphocyte; bone loss
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

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.