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Analysis of immune system in Mycobacterium tuberculosis-infected lung and vaccine development.

Research Project

Project/Area Number 16590365
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionUniversity of the Ryukyus

Principal Investigator

MATSUZAKI Goro  University of the Ryukyus, Center of Molecular Biosciences, Professor, 遺伝子実験センター, 教授 (30229455)

Co-Investigator(Kenkyū-buntansha) ARAKAWA Takeshi  University of the Ryukyus, Center of Molecular Biosciences, Associate Professor, 遺伝子実験センター, 助教授 (50305190)
UMEMURA Masayuki  University of the Ryukyus, Center of Molecular Biosciences, Assistant Professor, 遺伝子実験センター, 助手 (90359985)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsPulmonary tuberculosis / Protective immunity / T cell / T cell receptor / transgenic mouse / Th1
Research Abstract

In this research, we analyzed kinetics of mycobacterial Ag-specific CD4^+ T cells response in the Mycobacterium tuberculosis-(Mtb)-infected lung of mice. To detect mycobacterial Ag-specific T cells, we used transgenic mice (P25-TCR Tg mice) expressing T cell receptor (TCR) from CD4^+ T cells specific for mycobacterial Ag85B. In the first series of experiments, we transferred the transgenic CD4^+ T cells into wild type mice, then intratracheally infected the mice with Mtb. Although the transferred transgenic T cells were specific to mycobacterial Ag, we failed to detect clear Th1 response of the transgenic T cells in the Mtb-infected lung and its draining lymph nodes. We hypothesized that transferred transgenic T cells were not detected in the lung because T cell response in the lung delays compared to other sites, and transferred T cells failed to proliferate during the analysis. This may be resulted in dilution of transferred T cells by newly emigrated T cells from thymus during the a … More ssay. To address the possibility, we next infected P25-TCR Tg mice themselves. Th1-type immune response of the transgenic CD4^+ T cells was not detected in the lung draining lymph nodes and the lung infiltrating cells until more than 2 weeks after Mtb lung infection. Ag85B-expressing attenuated bacteria, M.bovis BCG, also failed to induce Th1 response in the lung of P25-TCR Tg mice at early stage of infection. On the other hand, subcutaneous infection of BCG induced Th1 response in the draining inguinal and popliteal lymph nodes from day 3 after inoculation. This demonstrates that P25-TCR Tg mice can develop Th1 type immune response to Ag85B quickly outside the lung. All the results suggest that protective immune response against Mtb delays in the lung. This may support establishment of pulmonary tuberculosis especially when protective immune response is not induced in the lung immune system. Although the mechanism of the retardation of lung immune response is not yet clearly identified, further information on the mechanism may support development of new vaccine targeted to the lung to induce protective immunity against pulmonary tuberculosis. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (22 results)

All 2006 2005 2004

All Journal Article (22 results)

  • [Journal Article] Suppressor of cytokine signalling-1 in lymphocytes regulates the development of intestinal inflammation in mice.2006

    • Author(s)
      Inagaki-Ohara, K.他
    • Journal Title

      Gut 55

      Pages: 212-219

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intraepithelial lymphocytes express junctional molecules in murine small intestine.2005

    • Author(s)
      Inagaki-Ohara, K. 他
    • Journal Title

      Biochem. Biophys. Res. Comm. 331

      Pages: 977-983

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fas ligand induces cell-autonomous IL-23 production in dendritic cells, a mechanism for Fas ligand-induced IL-17 production.2005

    • Author(s)
      Kidoya, H. 他
    • Journal Title

      J. Immunol. 175

      Pages: 8024-8031

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intraepithelial lymphocytes express junctional molecules in murine small intestine.2005

    • Author(s)
      Inagaki-Ohara, K. et al.
    • Journal Title

      Biochem.Biophis.Res.Comm. 331

      Pages: 977-983

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fas ligand induces cell-autonomous IL-23 production in dendritic cells, a mechanism for Fas ligand-induced IL-17 production.2005

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

      J.Immunol. 175

      Pages: 8024-8031

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fas ligand induces cell-autonomous IL-23 production in dendritic cells, a mechanism for Fas ligand-induced IL-17 production2005

    • Author(s)
      Kidoya, H.他
    • Journal Title

      Journal of Immunology 175

      Pages: 8024-8031

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nasal immunization with a malaria transmission-blocking vaccine candidate Pfs25 induces complete protective immunity in mice against field-isolated Plasmodium falciparum.2005

    • Author(s)
      Arakawa, T.他
    • Journal Title

      Infection and Immunity 73

      Pages: 7375-7380

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Heteropentameric cholera toxin B subunit chimeric molecules genetically fused to a vaccine antigen induce systemic and mucosal immune responses : a potential new strategy to target recombinant vaccine antigens to mucosal immune systems.2005

    • Author(s)
      Harakuni, T. 他
    • Journal Title

      Infection and Immunity 73

      Pages: 5654-5665

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mucosal T cells bearing γδT-cell receptor play a protective role in intestinal inflammation2004

    • Author(s)
      Inagaki-Ohara, K. 他
    • Journal Title

      Journal of Immunology 173

      Pages: 5156-5164

    • 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 IL-17 in Fas ligand-induced inflammation2004

    • Author(s)
      Umemura, M. 他
    • Journal Title

      International Immunology 16

      Pages: 1099-1018

    • NAID

      10013425139

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vδl^1 γδ T cells producing CC chemokines may bridge a gap between neutrophils and macrophages in innate immunity during Eschericha coli infection in mice2004

    • Author(s)
      Tagawa, T. 他
    • Journal Title

      Journal of Immunology 173

      Pages: 5156-5164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Recombinant Ascaris 16-kDa protein induces protection against Ascaris suum larval migration following intranasal vaccination in pigs2004

    • Author(s)
      Tsuji, N 他
    • Journal Title

      Journal of Infectious Disease 190

      Pages: 1812-1820

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mucosal T cells bearing γδT-cell receptor play a protective role in intestinal inflammation2004

    • Author(s)
      Inagaki-Ohara, K. et al.
    • Journal Title

      J.Immunol. 173

      Pages: 5156-5164

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of IL-17 in Fas ligand-induced inflammation2004

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

      Int.Immunol 16

      Pages: 1099-1018

    • NAID

      10013425139

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vδ1^+ γδ T cells producing CC chemokines may bridge a gap between neutrophils and macrophages in innate immunity during Eschericha coli infection in mice2004

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

      J.Immunol. 173

      Pages: 5156-5164

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Recombinant Ascaris 16-kDa Protein induces protection against Ascaris suum larval migration following intranasal vaccination in pigs2004

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

      J.Infect.Dis. 190

      Pages: 1812-1820

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mucosal T cells bearing γδT-cell receptor play a protective role in intestinal inflammation2004

    • Author(s)
      Inagaki-Ohara, K.他
    • Journal Title

      Journal of Immunology 173

      Pages: 5156-5164

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of IL-17 in Fas ligand-induced inflammation2004

    • Author(s)
      Umemura, M.他
    • Journal Title

      International Immunology 16

      Pages: 1099-1018

    • NAID

      10013425139

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Vδ1^+γδ T cells producing CC chemokines may bridgea a gap between neutrophils and macrophages in innate immunity during Eschericha coli infection in mice2004

    • Author(s)
      Tagawa, T.他
    • Journal Title

      Journal of Immunology 173

      Pages: 5156-5164

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Recombinant Ascaris 16-kDa protein induces protection against Ascaris suum larval migration following intranasal vaccination in pigs2004

    • Author(s)
      Tsuji, N他
    • Journal Title

      Journal of Infectious Disease 190

      Pages: 1812-1820

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intranasal sensitization with Blomia tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum IgE and peripheral blood eosinophil counts2004

    • Author(s)
      Takeda F他
    • Journal Title

      Rev.Inst.Med.Trop.Sao Paulo 66

      Pages: 1-8

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Temperature and metal ions-dependent activity of the family I inorganic pyrophosphatase from the swine roundworm Ascaris suum2004

    • Author(s)
      Islam MK, 他
    • Journal Title

      J.Vet.Med.Sci. 66

      Pages: 221-223

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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