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Keywords:

  • Osteoclast;
  • IFN-γ;
  • RANKL;
  • T cell;
  • Th1

Abstract

The current study explored our hypothesis that IFN-γ-producing human T cells inhibit human osteoclast formation. Activated T cells derived from human PBMC were divided into IFN-γ-producing T cells (IFN-γ+ T cells) and IFN-γ-non-producing T cells (IFN-γ T cells). IFN-γ+ T cells were cultured with human monocytes in the presence of macrophage-CSF alone. The concentration of soluble receptor activator of NF-κB ligand (RANKL) and IFN-γ, and the amount of membrane type RANKL expressed on T cells, were measured by ELISA. In the patients with early rheumatoid arthritis (RA) treated with non-steroidal anti-inflammatory drugs alone, CD4+ T cells expressing both IFN-γ and RANKL were detected by flow cytometry. Surprisingly, IFN-γ+ T cells, but not IFN-γ T cells, induced osteoclastogenesis from monocytes, which was completely inhibited by adding osteoprotegerin and increased by adding anti-IFN-γ antibodies. The levels of both soluble and membrane type RANKL were elevated in IFN-γ+ T cells. The ratio of CD4+ T cells expressing both IFN-γ and RANKL in total CD4+ T cells from PBMC was elevated in RA patients. Contrary to our hypothesis, IFN-γ+ human T cells induced osteoclastogenesis through the expression of RANKL, suggesting that Th1 cells play a direct role in bone resorption in Th1 dominant diseases such as RA.