• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Activated T cells induce osteoclastogenesis in rheumatoid arthritis.

Research Project

Project/Area Number 13670480
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionTokyo Women's Medical University

Principal Investigator

KOTAKE Shigeru  Tokyo Women's Med.Univ., Assistant Prof., 医学部, 講師 (00234774)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsrheumatoid arthritis / T cells / osteoclast / interferon-gamma / RANKL / Th1 / osteoprotegerin / osteoarthritis / osteoprotegerin / 慢性関節リウマチ / OPG / Tリンパ球
Research Abstract

We previously demonstrated that activated human T cells expressing the receptor activator of NF-κB (RANKL) directly induce osteoclastogenesis from human monocytes. The current study explored our hypothesis that IFN-γ-producing T cells inhibit osteoclast formation.
Activated T cells derived from human peripheral blood 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 or IFN-γ(-) T cells were cultured with human monocytes from PBMC in the presence of M-CSF alone. The expression of IFN-γ, IL-4, or RANKL on T cells was detected by flow cytometry. The concentration of soluble RANKL or IFN-γ and the amount of membrane type RANKL expressed on T cells were measured by ELISA. In 15 patients with RA treated with NSAIDs alone and not receiving DMARDs or prednisone and 11 patients with OA, 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 in the presence of M-CSF alone, which was completely inhibited by adding osteoprotegerin. In addition, the osteoclastogenesis induced by IFN-γ(+) T cells was increased by adding anti-IFN-γ antibodies. IFN-γ(+) T cells included T cells identified as Th1 cells by flow cytometry. In addition, 100pg/ml of IFN-γ, which was a sufficient concentration to inhibit osteoclastogenesis, was detected in the culture supernatants of IFN-γ(+) T cells by ELISA. 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 peripheral blood was significantly higher in RA patients than in OA patients.
Contrary to our hypothesis, these findings demonstrated that IFN-γ(+) T cells induce osteoclastogenesis through the expression of RANKL, suggesting that Th1 cells play a direct role in bone resorption in Th1 dominant diseases such as RA.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] 小竹 茂: "関節リウマチに伴う破骨細胞形成活性化におけるT細胞の役割"Osteoporosis Japan. 12. 83-88 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeru KOTAKE: "The roles of activated T cells in osteoclastogenesis of patients with rheumatoid arthritis"Osteoporosis Japan. vol.12, no.1. 83-88 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kotake S et al.: "Activated human T cells directly induce osteoclastogenesis from human monocytes : possible role of T cells in destruction in rheumatoid arthritis patients"Arthritis & Rheumatism. 44(5). 1003-1012 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kotake S, et al.: "Activated human T cells directly induce osteoclastogenesis from human monocytes : possible role of T cells in bone destruction in rheumatoid arthritis patients"Arthritis Rheum.. 44(5). 1003-12 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi