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Importance of hepatic lymphocytes on innate immunity

Research Project

Project/Area Number 14370162
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionNiigata University

Principal Investigator

ABO Toru  Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (30005079)

Co-Investigator(Kenkyū-buntansha) SEKIKAWA Hiroho  Niigata University, Institute of Medicine and Dentistry, Associate Professor, 医歯学系, 助教授 (50018694)
WATANABE Hisami  University of the Ryukyus, Center of Molecular Biosciences Immunobiology Group, Professor, 遺伝子実験センター, 教授 (50143756)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsautoimmune disease / extrathymic T cells / B-1 cell / human liver lymphocyte / B-2 cell / liver transplantation / NZB / WF_1 mice / malaria
Research Abstract

Malarial parasites are intracellular pathogens and therefore invade erythrocytes and hepatocytes. In this respect, conventional T and B cells could not function against the parasites. Inversely, extrathymic T cells and B-1 cells attack such parasites by their autoreactivity and autoantibodies. These evidences were produced in both murine and human studies. We also found that erythropoiesis was induced in the liver of mice after malarial infection. It is speculated that fresh erythrocytes produced in the liver might be an important target for the parasites. TAP-1(-/-) mice with missing self were also used in this study and extrathymic T cells were abundant in these mice. Innate immunity mediated by extrathymic T cells is found to be importance to eliminate missing self. A similar phenomenon was also seen in mice with stress and in mice with amyloidosis. Granulocytes are also important in parallel with extrathymic T cells and B-1 cells. In 2004, anti-erythropoietin antibody was found to cure malaria when injected into mice with malaria. In 2005 final year, the activation of NKT cells by α-GalCer induced hepatic failure. This result indicated that overactivation of NKT cells is able to induce tissue damage. NK1.1-TCR^<int> cells are also found to be a major lymphocyte subset in malarial infection.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (41 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (29 results) Publications (12 results)

  • [Journal Article] Reasons why DBA/2 mice are resistant to malarial infection : expansion of CD3^<int>B220^+γδT cells with double-negative CD4^-8^- phenotype in the liver.2006

    • Author(s)
      Bakir, H.Y.et al.
    • Journal Title

      Immunology 117

      Pages: 127-135

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Protection against malaria due to innate immunity enhanced by low-protein diet.2006

    • Author(s)
      Ariyasinghe, A. et al.
    • Journal Title

      J.Parasitol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Protection against malaria due to innate immunity enhanced by low-protein diet.2006

    • Author(s)
      Ariyasinghe, A. et al.
    • Journal Title

      J.Parasitol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] No mixing of granulocytes and other lymphocytes in the inflamed joints of parabiosis mice with collagen-induced arthritis : possible in situ generation.2005

    • Author(s)
      Nishizawa, T. et al.
    • Journal Title

      Immunology 114

      Pages: 133-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Immunologic states of autoimmune diseases.2005

    • Author(s)
      Abo, T.et al.
    • Journal Title

      Immunol.Res. 33

      Pages: 23-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoietis in the liver and other sites.2005

    • Author(s)
      Tsubata, S. et al.
    • Journal Title

      Immunol.Cell Biol. 83

      Pages: 638-642

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoiesis in the liver and other sites.2005

    • Author(s)
      Tsubata, S. et al.
    • Journal Title

      Immunol.Cell Biol. 83

      Pages: 638-642

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Age-related bias in function of natural killer T cells and granulocytes after stress : reciprocal association of steroid hormones and sympathetic nerves.2004

    • Author(s)
      Sagiyama, K. et al.
    • Journal Title

      Clin.Exp.Immunol. 135

      Pages: 56-63

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of natural killer T cells and granulocytes in the inflammation induced by partial hepatectomy.2004

    • Author(s)
      Kato, T. et al.
    • Journal Title

      J.Hepatol. 40

      Pages: 285-290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Generation of B220^<low> B cells and production of autoantibodies in mice with experimental amyloidosis : association of primordial T cells with this phenomenon.2004

    • Author(s)
      Kawabe, S. et al.
    • Journal Title

      Clin.Exp.Immunol. 135

      Pages: 200-208

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis.2004

    • Author(s)
      Saito, T. et al.
    • Journal Title

      J.Immunol. 173

      Pages: 579-585

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Granulocytic activation and reciprocal immunosuppression induced by dehydration : relationship with renal failure.2004

    • Author(s)
      Tsuchida, M. et al.
    • Journal Title

      Biomed.Res. 25

      Pages: 171-178

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Comparative characterization of double-positive CD4^+8^+ cells in the thymus and small intestine of mice.2004

    • Author(s)
      Ebe, K.et al.
    • Journal Title

      Biomed.Res. 25

      Pages: 201-207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially natural killer T cells, double-positive CD4^+CD8^+ cells and B220^+T cells, in mice.2004

    • Author(s)
      Ishimoto, Y. et al.
    • Journal Title

      Immunology 113

      Pages: 371-377

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Expansion of NK1.1^- intermediate TCR cells and granulocytes in mice transplanted with TAP-1-deficient cells.2004

    • Author(s)
      Izumi, N. et al.
    • Journal Title

      Biomed.Res. 25

      Pages: 209-218

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis.2004

    • Author(s)
      Saito, T. et al.
    • Journal Title

      J.Immunol 173

      Pages: 579-585

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Comparative characterization of double-positive CD4^+8^+ cells in the thymus and small intestine of mice.2004

    • Author(s)
      Ebe, K.et al.
    • Journal Title

      Biomed.Res. 113

      Pages: 201-207

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expansion of NK1.1^- intermediate TCR cells and granulocytes in mice transplanted with TAP-1-deficient cells.2004

    • Author(s)
      Izumi, N.et al.
    • Journal Title

      Biomed.Res. 25

      Pages: 209-218

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expansion of unconventional T cells with natural killer markers in malaria patients.2003

    • Author(s)
      Watanabe, H. et al.
    • Journal Title

      Parasitol.Int. 52

      Pages: 61-70

    • NAID

      50000738992

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of extrathymic CD8αβ T cells in the liver and intestine of TAP-1 deficient mice.2003

    • Author(s)
      Tsukada, C. et al.
    • Journal Title

      Immunology 109

      Pages: 343-350

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Onset of hepatic erythropoiesis after malarial infection in mice.2003

    • Author(s)
      Halder, R.C. et al.
    • Journal Title

      Parasitol.Int. 52

      Pages: 259-268

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association of CD8^+ natural killer T cells in the liver with neonatal tolerance phenomenon.2002

    • Author(s)
      Kawamura, H, et al.
    • Journal Title

      Transplantation 73

      Pages: 978-994

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Liver injury due to sequential activation of natural killer cells and natural killer T cells by carrageenan.2002

    • Author(s)
      Abe, T.et al.
    • Journal Title

      J.Hepatology 36

      Pages: 614-623

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Essential role of extrathymic T cells in protection against malaria.2002

    • Author(s)
      Mannoor, M.K. et al.
    • Journal Title

      J.Immunol. 169

      Pages: 301-306

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Simultaneous activation of natural killer T cells and autoantibody production in mice injected with denatured syngeneic liver tissue.2002

    • Author(s)
      Naito, T. et al.
    • Journal Title

      Clin.Exp.Immunol. 129

      Pages: 397-404

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Unconventional NK1.1^- intermediate TCR cells as major T lymphocytes expanding in chronic graft-versus-host disease.2002

    • Author(s)
      Miyakawa, R. et al.
    • Journal Title

      Eur.J.Immunol. 32

      Pages: 2521-2531

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tissue-specific expansion of NKT and CD5^+B cells at the onset of autoimmune disease in (NZB×NZW)F_1 mice.2002

    • Author(s)
      Morshed, S.R.M.et al.
    • Journal Title

      Eur.J.Immunol. 32

      Pages: 2551-2561

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association of CD8^+ natural killer T cells in the liver with neonatal tolerance phenomenon.2002

    • Author(s)
      Kawamura, H. et al.
    • Journal Title

      Transplantation 73

      Pages: 978-994

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tissue-specific expansion of NKT and CD5^+B cells at the onset of autoimmune disease in (NZB×NZW) F_1 mice.2002

    • Author(s)
      Morshed, S.R.M.et al.
    • Journal Title

      Eur.J.Immunol. 32

      Pages: 2551-2561

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Watanabe, H. et al.: "Expansion of unconventional T cells with natural killer markers in malaria patients"Parasitol.Int.. 52. 61-70 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsukada, C. et al.: "Characterization of extrathymic CD8αβ T cells in the liver and intestine of TAP-1 dificient mice"Immunology. 109. 343-350 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Halder, R.C. et al.: "Onset of hepatic erythropoiesis after malarial infection in mice"Parasitol.Int.. 52. 259-268 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sagiyama, K. et al.: "Age-related bias in function of natural killer T cells and granulocytes after stress : reciprocal association of steroid hormones and sympathetic nerves"Clin.Exp.Immunol.. 135. 56-63 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato, T. et al.: "Involvement of natural killer T cells and granulocytes in the inflammation induced by partial hepatectomy"J.Hepatol.. 40. 285-290 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawabe, S.et al.: "Generation of B220^<low> B cells and production of autoantibodies in mice with experimental amyloidosis : association of primordial T cells with this phenomenon"Clin.Exp.Immunol.. 135. 200-208 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Eawamura, H., et al.: "Association of CD8^+ natural killer T cells in the liver with neonatal tolerance phenomenon"Transplantation. 73. 978-994 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Abe, T., et al.: "Liver injury due to sequential activation of natural killer cells and natural killer T cells by carrageenan"J.Hepatology. 36. 614-623 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mannoor, M.K., et al.: "Essential role of extranthymic T cells in protection against malaria"J.Immunol.. 169. 301-306 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Naito, T., et al.: "Simultaneous activation of natural killer T cells and autoantibody production in mice Injected with denatured syngeneic liver tissue"Clin.Exp.Immunol.. 129. 397-404 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyakawa, R., et al.: "Unconventional NK1.1^-intermediate TCR cells as major T lymphocytes expanding in chronic graft-versus-host desease"Eur.J.Immunol.. 32. 2521-2531 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morshed, S.R.M., et al.: "Tissue-specific expansion of NKT and CD5^+B cells at the onset of autoimmune disease in(NZB × NZW)E mice"Eur.J.Immunol.. 32. 2551-2561 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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