Nanke Yuki
   Department   School of Nursing, School of Nursing
   Position   Professor
Article types Original article
Language English
Peer review Peer reviewed
Title IFN-gamma-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKL.
Journal Formal name:European journal of immunology
Abbreviation:Eur J Immunol
ISSN code:(0014-2980)0014-2980(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 35(11),pp.3353-3363
Author and coauthor Kotake Shigeru, Nanke Yuki, Mogi Makio, Kawamoto Manabu, Furuya Takefumi, Yago Toru, Kobashigawa Tsuyoshi, Togari Akifumi, Kamatani Naoyuki
Publication date 2005/11
Summary The current study explored our hypothesis that IFN-gamma-producing human T cells inhibit human osteoclast formation. Activated T cells derived from human PBMC were divided into IFN-gamma-producing T cells (IFN-gamma(+) T cells) and IFN-gamma-non-producing T cells (IFN-gamma(-) T cells). IFN-gamma(+) T cells were cultured with human monocytes in the presence of macrophage-CSF alone. The concentration of soluble receptor activator of NF-kappaB ligand (RANKL) and IFN-gamma, 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-gamma and RANKL were detected by flow cytometry. Surprisingly, IFN-gamma(+) T cells, but not IFN-gamma(-) T cells, induced osteoclastogenesis from monocytes, which was completely inhibited by adding osteoprotegerin and increased by adding anti-IFN-gamma antibodies. The levels of both soluble and membrane type RANKL were elevated in IFN-gamma(+) T cells. The ratio of CD4+ T cells expressing both IFN-gamma and RANKL in total CD4+ T cells from PBMC was elevated in RA patients. Contrary to our hypothesis, IFN-gamma(+) 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.
DOI 10.1002/eji.200526141
PMID 16220542