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A Study of Autoreactive T Cells in Drug-Induced Autoimmune Skin Disease

Research Project

Project/Area Number 01570570
Research Category

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

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionYokohama City University

Principal Investigator

IKEZAWA Zenro  Yokohama City Uni. School of Medicine, Associate Professor, 医学部, 助教授 (90046128)

Co-Investigator(Kenkyū-buntansha) SASAKI Tetsuo  Yokohama City Uni. School of Medicine, Instructor, 医学部, 助手 (10170680)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsSulfhydril drug / GVHD-like drug eruption (reaction) / IFNgamma / TNFalpha / Epidermal Langerhans cell / HLA-DR of keratinocyte / BP antigen of keratinocyte / Slot blot hybridization / TNFα / 角化細胞のBP抗原 / SH薬剤 / 皮膚GVHD様変化 / 薬剤特異的TCPR / IL-2反応性試験 / SH薬剤パルス脾細胞
Research Abstract

1) In the drug eruptions, which were classified to the subgroup of acute cutaneous GVHD (graft-verusus-host disease) type from the clinicohistopathological findings, we observed the dominant infiltration of CD8+ T cells in the epidermis, depletion/reduction of CD1+ epidermal Langerhans cells and remarkable expression of HLA-DR/ICAM-1 on the kerationcytes. These findings are the same as acute cutaneous GVHD itself appeared after bone marrow transplantation and blood transfusion, indicating that essentially the same pathomechanism is involved in the both conditions, and also that enhancement of T cells with cytotoxic activity and the inflammatory cytokines such as IFNgamma and TNFalpha may play an important role in development of GVHD itself and GVHD-like reaction by drugs.
2) In the footpad reactions by local transfer of sulfhydril drug, tiopronin (TP)-sensitized lymph node cells (LC) and spleen cells (SC), IFNgamma and TNFalpha were also required for the full induction of GVHD-like reactions.
3) We have already revealed that IFNgamma, which is released from the activated T cells, enhances the expression of bullous pemphigoid (BP) antigen on the cultured keratinocytes by flow cytometory. In this study we revealed the enhanced expression of BP antigen in the messenger RNA levels by slot blot hybridization. These results reconfirmed the possibility that cytokines such as IFNgamma from the activated T cells might be involved in development of autoimmune bullous pemphigoid.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Ikezawa Z,Kitamura K,Nalajima H: "Gold sodium thiomalate (GTM) induces hypersensitivity to thiomalate,the thiol carrier of GTM" The Journal of Dermatology. 17. 550-554 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 大沢 純子: "SH薬剤感作マウスリンパ球の抗原刺激に対するILー2反応性の検討ー蛍光色素を用いた生細胞数迅速測定法の応用" 日本皮膚科学会誌. 100. 1235-1240 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Osawa J,Kitamura K,Ikezawa Z,Nakajima H: "A probable role of vaccines containing thimerosal in thimerosal hypersensitivity" Contact Dermatitis. 20. (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kitamura K,Osawa J,Ikezawa Z: "Crossーreactivity between hypersensitivity to thimerosal and photohyperaensitivity to piroxicam in guinea pigs" Contact Dermatitis. 20. (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suguta Y,Nagatani T,Ikezawa Z,Nomura K,Watanabe Y,Uitto J,Nakajima H: "Modification of bullous pemphigoid antigen protein and gene expression by γーinterferon" Journal of Investigative Dermtology. (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 北村 和子,大沢 純子,池沢 善郎,中嶋 弘: "SH基含有薬剤によるGVHD様反応の誘導に及ぼすIFNγとTNFαの効果" 日本皮膚科学会誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 池沢 善郎: "実験的薬疹" 現代皮膚科学大系、年刊版'88ーB、中山書店, 117-135 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ikezawa Z,Aihara M,and Kitamura K: "Drugーinduced rashes in guinea pigs" Models in Dermatology IV edited by Maibach HI and Lowe NJ,Karger,Basel, 79-95 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Aihara M, Ikezawa Z, Komatsu H, Nagatani T, Nakajima H: "Modification of lymphocyte proliferation test with human peripheral blood -Enhancement effect by adding IL-2 after antigen stimulation and rapid fluorochromasia assay-" Yokohama medicine. 39(4). 215-221 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Osawa J, Takahashi Y, Ikezawa Z: "A case of acute graftverusus-host disease resulting from autologous bone marrow transplantation" Jpn. Clin. Dermatol.42(6). 537-541 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Saito S, Miyamoto H, Kim S, Ikezawa Z, Nakajima H: "Immunological study of DDS syndrome" Jpn. Clin. Dermatol.43(13). 1267-1271 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ikezawa Z, Aihara M and Kitamura K: "Drug-induced rashes in guinea pigs" Models in Dermatology IV edited by Maibach HI and Lowe NJ, Karger, Basel.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kitamura K, Aihara M, Osawa J, Naito S, Ikezawa Z: "Sulfhydryl drug-induced eruption. A clinical and histological study" J. Dermatol.17(1). 44-51 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kitamura K, Aihara M, Ikezawa Z: "Generalized rash induced by sulfhydryl drug in guinea pigs -A comparative study on it with cephalothin-induced rash in guinea pigs-" J. Dermatol.17(3). 168-175 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Osawa J, Naito S, Aihara M, Kitamura K, Ikezawa Z, Nakajima H: "Evaluation of skin test reactions in patients with nonimmediate type drug eruptions" J. Dermatol.17(4). 235-239 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ikezawa Z, Kitamura K, Nakajima H: "Gold sodium thiomalate (GTM) induces hypersensitivity to thiomalate, the thiol carrier of GTM" J. Dermatol.17(9). 550-554 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Osawa J: "IL-2 responsiveness in antigen-specific lymphocyte proliferation test with sufhydril drug-sensitized murine lymphocytes -Using rapid fluorochromasia assay-" Jpn. J. Dermatol.100(12). 1235-1240 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Osawa J, Kitamura K, Ikezawa Z, Nakajima H: "A probable role of vaccines containing thimerosal in thimerosal hypersensitivity" Contact Dermatitis. 20. (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Saito S, Miyamoto H, Ikezawa Z: "A case of fixed drug eruption due to cyanamide with a flare-up reaction" Jpn. Clin. Dermatol.45(2). 143-146 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kitamura K, Osawa J, Ikezawa Z: "Cross-reactivity between hypersensitivity to thimerosal and photohypersensitivity to piroxicam in guinea pigs" Contact Dermatitis. 20. (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ikezawa Z, Kitamura K, Osawa J, Nakajima H, Hariya T: "Photosensitivity to piroxicam is induced by sensitization to thimerosal and thiosalicylate" J. Invest. Dermatol.(1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suguta Y, Nagatani T, Ikezawa Z, Nomura K, Watanabe Y, Uitto J, Nakajima H: "Modification of bullous pemphigoid antigen protein and gene expression by gamma -interferon" J. Invest. Dermatol.(1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kitamura K, Osawa J, Ikezawa Z, Nakajima H: "Effect of IFNgamma and TNFalpha on the induction of GVHD-like reactions by sulfhydril drugs" Jpn. J. Dermatol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ikezawa Z,Kitamura K,Nakajima H: "Gold sodium thiomalate(GTM)induces hypersensitivity to thiomalate,the thiol carrier of GTM" The Journal of Dermatology. 17. 550-554 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 大沢 純子: "SH薬剤感作マウスリンパ球の抗原刺激に対するILー2反応性の検討ー蛍光色素を用いた生細胞数迅速測定法の応用" 日本皮膚科学会誌. 100. 1235-1240 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Osawa J,Kitamura K,Ikezawa Z,Nakajima H: "A probable role of vaccines containing thimerosal in thimerosal hypersensitivity" Contact Dermatitis. 20. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kitamura K,Osawa J,Ikezawa Z: "Crossーreactivity between hypersensitivity to thimerosal and photohypersensitivity to piroxicam in guinea pigs" Contact Dermatitis. 20. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suguta Y,Nagatani T,Ikezawa Z,Nomura K,Watanabe Y,Uitto J,Nakajima H: "Modification of bullous pemphigoid antigen protein and gene expression by γーinterferon" Journal of Investigative Dermatology. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 北村 和子、大沢 純子、池沢 善郎、中嶋 弘: "SH基含有薬剤によるGVHD様反応の誘導に及ぼすIFNγとTNFαの効果" 日本皮膚科学会誌.

    • Related Report
      1990 Annual Research Report
  • [Publications] 池沢 善郎: "実験的薬疹" 現代皮膚科学大系、年刊版'88ーB、中山書店, 117-135 (1988)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ikezawa Z,Aihara M and Kitamura K: "Drugーinduced rashes in guinea pigs" Models in Dermatology IV edited by Maibach HI and Lowe NJ,Karger,Basel, (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kitamura,K.,Aihara,M.,Osawa,J.,Naito,S.and Ikezawa,Z.: "Sulfhydryl drug-induced eruption: A clinical and histological study" The Journal of Dermatolgy. 17. 44-51 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kitamura,K.,Aihara,M.and Ikezawa,Z.: "Generalized rash induced by sulfhydryl drug in guinea pigs-A comparative study on it with cephalothin-induced rash in guinea pigs-" The Journal of Dermatology. 17. 168-175 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 大沢純子: "SH薬剤感作マウスリンパ球の抗原刺激に対するIL2反応性の検討-蛍光色素を用いた生細胞数迅速想定法の応用-" 日本皮膚科学会誌.

    • Related Report
      1989 Annual Research Report
  • [Publications] 大沢純子,北村和子,池澤善郎,中嶋弘: "チオプロニン感作マウスの足蹠反応に及ぼすTNFαとIFNγの効果" 日本皮膚科学会誌.

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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