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Unusual increase of extrathymic T cells in the liver of autoimmune MRL-1pr/1pr mice.

Research Project

Project/Area Number 05454202
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

KUMAGAI Katsuo  Tohoku Univ. Dentistry ant Prof., 歯学部, 教授 (00005018)

Co-Investigator(Kenkyū-buntansha) HANAUMI Kiyoshi  Tohoku Univ. Dentistry Assist Prof., 歯学部, 助手 (50005063)
RIKIISHI Hidemi  Tohoku Univ. Dentistry Assist ant Prof., 歯学部, 助手 (70091767)
SUGAWARA Shunji  Tohoku Univ. Dentistry Assist ant Prof., 歯学部, 助手 (10241639)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsMRL / 1pr mice / IL-6 / ICAM-1 / Liver / Autoimmune disease / MRL-1prマウス / MRL-lpr / lprマウス
Research Abstract

MRL/1pr mice, which are a model of SLE and rheumatoid arthritis in humans, develop profound lymphadenopathy resulting from the accumulation of CD3^+ 4^- 8^- double-negative (DN) alpha beta T cells in peripheral lymphoid tissues. We previously indicated that these DN alpha beta T cells preferentially proliferate in the liver and migrate to the periphery. In this study, we analyzed whether any kind of cytokine was produced by hepatic mononuclear cells (MNC) in MRL/1pr mice. The evidence obtained indicates that interleukin 6 (IL-6) was vigorously produced by hepatic MNC in diseased MRL/1pr mice under unstimulated conditions. MNC in the spleen of these mice produced small amounts of IL-6, while those in the lymph nodes did not produce any appreciable amounts of IL-6. These activities of hepatic MNC in diseased MRL/1pr mice were almost completely neutralized by anti-mouse IL-6 monoclonal antibody (mAb).
On the other hand, immunohistochemical staining of light-and electron-microscopic analyzes revealed that the intracellular cell abhesion molecule 1 (ICAM-1) was expressed on the hepatic sinusoidal endothelial cells of diseased MRL/1pr mice. Moreover, ICAM-1 was newly induced in the hepatic sinusoids of control C3H/He mice by an intravenous injection of 50 units of recombinant mouse IL-6. These data suggest that ICAM-1 expressed on the hepatic sinusoidal endothelial cells in MRL/1pr mice is induced by IL-6, which is produced by hepatic MNC,and that such ICAM-1 may be responsible for the saturation of inflammatory cells and the proliferation of lymphocytes in the liver of MRL/1pr mice.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] T.Ohteki: "Age-associated increase of CD5^+B cells in the liver of autoimmune(NZB×NZW)F_1mice." Microbiol.Immunol.37. 221-228 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Ohteki: "Elevated production of interleukin 6 by hepatic MNC correlates with ICAM-1 expression on the hepatic sinusoidal endothelial cells in autoimmune MRL/lpr mice." Immunol.Letters. 36. 145-152 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Koyamada: "Induction of specific tolerance by hepatic double-negative CD48αβT cells of mice immunized with allogeneic cells via the portal vein in vitro." Cell.Immunol.149. 107-116 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Onta: "Induction of acute arthritis in mice by peptidoglycan derived from grampositive bacteria and its possible role in cytokine production." Microbiol.Immunol.37. 573-582 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Ando: "Stimulation of the synthesis of histamine and putrescine in mice by a peptidoglycan of gram-positive bacteria." Microbiol.Immunol.38. 209-215 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Endo: "Effects of macrophage depletion the induction of histidine decarboxylase by lipopolysaccharide,interleukin 1 and tumor necrosis factor." Br.J.Pharmacol.114. 187-193 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Ohteki: "Age-associated increase of CD5^+ B cells in the liver of autoimmune (NZB*NZW) F_1 mice." Microbiol. Immunol.37. 221-228 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Ohteki: "Elevated production of interleukin 6 by hepatic MNC correlates with ICAM-1 expression on the hepatic sinusoidal endothelial cells in autoimmune MRL/1pr mice." Immunol.Letters. 36. 145-152 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Koyamada: "Induction of specific tolerance by hepatic double-negative CD4^- 8^- alpha beta T cells of mice immunized with allogeneic cell via the portal vein in vitro." Cell. Immunol.149. 107-116 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Onta: "Induction of acute arthritis in mice by peptidoglycan derived from gram-positive bacteria and its possible role in cytokine production." Microbiol. Immunol.37. 573-582 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Ando: "Stimulation of the synthesis of histamine and putrescine in mice by a peptidoglycan of gram-positive bacteria." Microbiol. Immunol.38. 209-215 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Endo: "Effects of macrophage depletion on the induction of histidine decarboxylase by lipopolysaccharide, interleukin 1 and tumor necrosis factor." Br. J.Pharmacol.114. 187-193 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Ohteki: "Age-associated increase of CD5^+B cells in the liver of autoimmune(NZB×NZW)F_1 mice." Microbiol.Immunol.37. 221-228 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Ohteki: "Elevated production of interleukin 6 by hepatic MNC correlates with ICAM-1 expression on the hepatic sinusoidal endothelial cells in autoimmune MRL/1pr mice." Immunol.Letters. 36. 145-152 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Koyamada: "Induction of specific tolerance by hepatic double-negative CD4^-8^-αβT cells of mice immunized with allogeneic cells via the portal vein in vitro." Cell.Immunol.149. 107-116 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Onta: "Induction of acute arthritis in mice by peptidoglycan derived from grampositive bacteria and its possible role in cytokine production." Microbiol.Immunol.37. 573-582 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Ando: "Stimulation of the synthesis of histamine and putrescine in mice by a peptidoglycan of gram-positive bacteria." Microbiol.Immunol.38. 209-215 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Endo: "Effects of macrophage depletion on the induction of histidine decarboxylase by lipopolysaccharide,interleukin 1 and tumor necrosis factor." Br.J.Pharmacol.114. 187-193 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Endo: "Aminoalkylbisphosphonate,potent inhibitor of bone resorption,induce a prolonged stimulation of histamine synthesis and increase macrophages,granulocytes,and osteoclastsin vivo." Calcif.Tissue Int.52. 248-254 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Ohteki: "Age-associated increase of CD5^+ B cells in the liver of autoimmune(NZB × NZW)F_1 mice." Microbiol.Immunol.37. 221-228 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Ohteki: "Elevated production of interleukin 6 by hepatic MNC correlates with ICAM-1 expression on the hepatic sinusoidal endothelial cells in autoimmune MRL/lpr mice." Immunol.Letters. 36. 145-152 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Koyamada: "Induction of specific tolerance by hepatic double-negative CD4^-8^- α β T cells of mice immunized with allogeneic cells via the portal vein in vitro" Cellular Immunol.149. 107-116 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Onta: "Induction of acute arthritis in mice by peptidoglycan derived from gram-positive bacteria and its possible role in cytokine production." Microbiol.Immunol.37. 573-582 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Sato: "Cytoplasmic membrane-associated protein(CAP)isolated from Streptococcus pyogenes:as a new bacterial superantigen." Microbiol.Immunol.38. 139-147 (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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