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Elucidation of function of cholera toxin as a mucosal adjuvant in salivary IgA production to T-cell independent antigen

Research Project

Project/Area Number 17592179
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Social dentistry
Research InstitutionOsaka University

Principal Investigator

KATAOKA Kosuke  Osaka University, Graduate school of dentistry, assistant professor, 大学院歯学研究科, 助手 (50283792)

Co-Investigator(Kenkyū-buntansha) OJIMA Miki  Osaka University, Graduate school of dentistry, assistant professor, 大学院歯学研究科, 助手 (20263303)
NAGATA Hideki  Osaka University, Graduate school of dentistry, associate professor, 大学院歯学研究科, 助教授 (50260641)
林 直治  大阪大学, 歯学部附属病院, 助手 (10303984)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsmucosal immunity / nasal immunization / salivary IgA / nasal adjuvant / Bl B cells / innate immunity / T cell independent antigen / IL-5 / B1B細胞 / アジュバント / B細胞
Research Abstract

In this study, we examined whether native cholera toxin (nCT) as a nasal adjuvant could support' trinitrophenyl (TNP)-lipopolysaccharide (LPS)-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. On 5 days after immunization, significantly higher levels of TNP-specific mucosal IgA antibody (Ab) responses were induced in the nasal washes, sal iva and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. In addition. Enhanced IgG3 and IgM Ab in the plasma of mice given nCT plus TNP-LPS were also seen. High numbers of TNP-specific IgA Ab forming cells (AFCs) were also detected in mucosal tissues such as the nasal passages (NPs), the submandibular glands (SMGs) and nasopharyngeal-associated lymphoreticular tissue of mice given nCT. In the flow cytometric analysis, higher numbers of surface IgA^+,CD5^+ B cells (B-la B cells) in SMGs and NPs of mice given nasal TNP-LPS plus nCT than in those given TNP-LPS alone were seen. Further, increased levels of IL-5 receptor α chain (IL-5Rα) were expressed by B-la B cells in SMGs and NPs of mice given nasal TNP-LPS plus nCT. Thus. CD4^+ T cells from these mucosal effector lymphoid tissues produce high levels of IL-5 at both protein and mRNA levels. When mice were treated with anti-IL-5 monoclonal Ab, significant reductions in TNP-specific mucosal IgA Ab responses were noted in external secretions. These findings show that nasal nCT as an adjuvant enhances mucosal immune responses to a T cell independent antigen due to the cross-talk between IL-5Rα^+ B-la B cells and IL-5 producing CD4^+T cells in the mucosal effector lymphoid tissues.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (9 results)

All 2007 2006 2005

All Journal Article (8 results) Book (1 results)

  • [Journal Article] Nasal chorela toxin elicits IL-5 and IL-5 receptor α chain expressing B-1a B cells for innate mucosal IgA antibody responses.2007

    • Author(s)
      Kataoka K. et al.
    • Journal Title

      Journal of Immunology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nasal chorela toxin elicits IL-5 and IL-5 receptor α chain expressing B-la B cells for innate mucosal IgA antibody responses.2007

    • Author(s)
      Kataoka K. et al.
    • Journal Title

      Journal of Immunology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A second generation of double mutant cholera toxin adjuvants : Enhanced immunity without intracellular trafficking.2006

    • Author(s)
      Hagiwara Y. et al.
    • Journal Title

      Journal of lmmunology 177(5)

      Pages: 3045-3054

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A second generation of double mutant cholera toxin adjuvants : Enhanced immunity without intracellular trafficking.2006

    • Author(s)
      Hagiwara Y. et al.
    • Journal Title

      Journal of Immunology 177(5)

      Pages: 3045-3054

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A second generation of double mutant cholera toxin adjuvants : Enhanced immunity without intracellular trafficking.2006

    • Author(s)
      Hagiwara Yukari et al.
    • Journal Title

      Journal of Immunology 177(5)

      Pages: 3045-3054

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Protective immunity against Streptococcus Pyogenes challenge in mice after immunization with fibronectin-binding protein.2005

    • Author(s)
      Terao Yutaka
    • Journal Title

      Journal of Infectious Disease 192

      Pages: 2081-2091

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nasal IL-12p70 DNA prevents and treats intestinal allergic diarrhea.2005

    • Author(s)
      Hino Ayako
    • Journal Title

      Journal of Immunology 174(11)

      Pages: 7423-7432

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel neurotoxoid vaccine prevents mucosal botulism2005

    • Author(s)
      Kobayashi Ryoki
    • Journal Title

      Journal of Immunology 174(4)

      Pages: 2190-2195

    • Related Report
      2005 Annual Research Report
  • [Book] 臨床免疫・アレルギー科 : コレラトキシンの粘膜投与によるIgA産生B細胞の誘導2007

    • Author(s)
      片岡 宏介等
    • Publisher
      科学評論社(In press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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