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Induction of tolerance of contact hypersensitivity by blocking CD28 Signal

Research Project

Project/Area Number 08670952
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YOKOZEKI Hiroo  Tokyo Med.Dental University, Associate professor, 医学部, 助教授 (90210608)

Co-Investigator(Kenkyū-buntansha) HATSUNAGA Tsuyoshi  Tokyo Med.Dept of Dermatology, Assistant, 医学部, 助手 (50239050)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsLangerhans cells / Contact allergy / B7 antigen / Cytokines / atopic dermatitis / CD80 / CD86 / cytokine
Research Abstract

1) The B7 nolecules expression in AD and CD
In the present study, we investigated the expression and function of co-stimulatory molecules in AD and CD.These molecules were not detected in normal control subjects. In non-lesional skin of atopic dermatits, CD86 but not CD80 was detected. Inlesional atopic dermatits, CD80 was expressed 42%, while CD86 was expressed in all case. Similar results of the stronger expression of CD86 over CD80 was detected in the lesional skin in CD.We conducted the inhibition test. Anti-CD86 mab completely inhibite T cell proliferation stimulated with crude extract of DP in the epidermal cell as antigen presenting cells.
These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of AD and CD.
2) In vitro
The hapten, TNBS,induced weak B7-1 (CD80) and moderate B7-2 (CD86) expression on Langerhans cells and mRNA expression of both molecules in organ-cultured murine skin. The intradermal injection of haptenated EC induced hapten-specific contact sensitivity.
When hapten-treated EC were injected into mice after incubation with anti-B7-2 (CD86) or B7-1 (CD80) antibody the resultant contact sensitivity reaction was decreased to less than 50% of the control reaction. Anti-B7-2 and antiB7-1mAb also inhibited hapten-specific lymphocyte proliferation or the allogeneic mixed lymphocyte reaction in vitro.
These data indicated that costimulatory signals induced by a hapten on Langerhans cells play an important roles in the induction of contact sensitivity in mice.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Yokozeki H et al.: "IFN-γ differentially regulates CD80 and CD86 expression on human Langerhan cells" Brit J.Dermatol. 136. 831-837 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohki O et al.: "The functional CD86 is predominantly expressed on Langerhan cells in atopic dermatitis" Brit J.Dermatol. 136. 838-845 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Katayama I et al.: "Blockade of costimulatory molecules CD 80 andCD86 down regulat induction of contact sensitivity by haptenated Epidermal-cells" Brit J.Dermatol. 136. 846-852 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoh T et al.: "Cyciophosphamide-induced brood and tissue eus nophilia in contact sensitibity:mechanism of haptenated-inuced eosinophl recurt rat" Eur J.Immunol. 27. 85-91 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igawa K et al: "Topical glucocorticoid augment both allergic and no-allergic cutaneous reaction in mice when applied at the a Heut C of CD" Allergology Intorn. 46. 33-41 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arimura Metal: "Expeerimental study for the Development of an in vitro test for contact allergen:II compotion study" Int Arch Allergy Imunol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 横関 博雄: "サイトカインとアレルギー" メティカム・ビュー社, 187-192 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 横関 博雄: "自己免疫性皮膚疾患:免疫疾患-分子メカニズムから病〓診断治療まで" 羊工者, 136-137 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokozaki H,Katayama I,Ohki O,Matsunaga T,Watanabe K,Satho Tm asuma M,Okumura K,Nishioka K: "Functional CD86 (B7-2/B70) on cultured human Langerhans cells" J Invest Dermatol. 106. 147-153 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsunaga T,Katayama I,Yokozeki H,Nishioka K: "ICAM-1 ex pression on keratinocyte in mechanically injured skin in patients with atopic dermatitis" J Dermatol Sci. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsunaga T,Katayama I,Yokozeki H,Nishioka K: "Superantigen-induced cytokine expression in oregan-cultured human skin" J Dermatol Sci. 11. 104-110 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokozeki H,Katayama I et al: "Interferon gamma defferentially regulates CD80 and CD86 expression on human Langerhas cells" Bri.J.Dermatol. 136. 831-837 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohki O,Yokozeki H et al.: "The functional CD80 is predominantly expressed on Langerhans cells in atopic dermatitis" Bri.J.Dermatol. 136. 838-845 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Katayama I,Matsunaga T,Yokozeki H et al.: "Blokade of costimularory molecules CD80 and CD86 down regulates induction of contact sensitivity by haptenated epidermal cells" Brit.J.Dermatol. 136. 846-852 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoh T et al.: "Cyclophosphamide-induced blood and tissue eosinophilia in contact sensitivity : mechanism of hapten-induced eosinophil recuruitment into the skin" Eur.J.Immunol. 27. 85-91 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igawa K,Katayama I,Minatohara K,Satoh T,Yokozeki H,Nishioka K: "Topical glucocorticoid augments both allergic and non-allergic cutaneous reaction in mice when applied at the afferent stage of contact sensitivity" Allergology Intern. 46. 33-41 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arimura M,Yokozeki H et al: "Experimental Study for the Development of an in vitro test for contact allergens, II.Comparison of the in vitro sensitization test with the guinea pig maximization test for contact allergens" Int Arch Allergy Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokozeki H et al: "IFN‐γ differntially regulate CD80andCD86 expression on human Langehan alls" Brit J.Dermatol. 136. 831-837 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohki.O et al: "The functional CD80 is preanriantly expressed on langeshans all in atopic dirmat,t,J" Brit.J.Dermotol. 136. 838-845 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Katayama I et al.: ":Blockccde of costimulatory moleales CD80 and CD86 down rejulated induction of Contact sensitivity by haptenatl F C" Brit.J.Dermotol. 136. 846-852 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Satoh T et al: "Cycloshos rhamide-indudd. blood and tissue . eosinoplil in contact glusitirity-mechansm of haptenatd-induct eosinopblieu" Eu J.Iwnunol. 27. 85-91 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Igawa K et al: "Topical gluco corticoid augments both allegic and nunallirgic cutcneous readia in mice when arplied at the aftait stagy of CI" Allergology Intern. 46. 33-41 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arimura M al: "Eperimental Stady for the Deuslopment of an in vido Ast for contact allengen II componsu study" Int Arch allergej Iiumurol (inpress).

    • Related Report
      1997 Annual Research Report
  • [Publications] 横関博雄: "サイトカンとアレルギー" メディカル レビュー社, 187-192 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 横関博雄: "自己免疫性皮膚疾患:免疫疾患-分子メカニズムから疾患診断診療まで" 羊工社, 136-137 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yokozeki H,et al: "Interferon gamma differentially regulates CD80 and CD86 expression on human Langerhans cells" Bri.J.Dermatol. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohki O,Yokozeki H et al: "The functional CD80 is predominantly expressed on Langerhans cells in atopic dermatitis" Bri.J.Dermatol. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Katayama I et al: "Blokade of costimulatory molecules CD80 and CD86 down regulates induction of contact sensitivity by haptenated EC" Bri.J.Dermatol. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokozeki H,Katayama I et al: "Functiona CD86 (B7-2) on cultured human Langerhans cells" J.Invest.Dermatol.106. 147-153 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokozeki H et al: "Experimental Study for the Development of an in vitro Test for Contact allergens" Int Arch Allergy Immunol,. 106. 394-400 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 横関博雄: "アトピー性皮膚炎:病態と治療" 医薬ジャーナル, 36-52 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 横関博雄: "サイトカインとアレルギー" メデカルレビュー社, 187-192 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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