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The role for intraepidermal T cells as innate immune cells

Research Project

Project/Area Number 13470175
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKyorin University

Principal Investigator

SHIOHARA Tetsuo  Kyorin University, School of Medicine, Professor, 医学部, 教授 (10118953)

Co-Investigator(Kenkyū-buntansha) HAYAKAWA Jun  Kyorin University, School of Medicine, Assistant, 医学部, 助手 (30255393)
MIZUKAWA Yoshiko  Kyorin University, School of Medicine, Assistant, 医学部, 助手 (50301479)
TERAKI Yuichi  Kyorin University, School of Medicine, Lecturer, 医学部, 講師 (10188667)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥8,200,000 (Direct Cost: ¥8,200,000)
KeywordsInnate immunity / fixed drug eruiption / intraepidermal T cells / NK cells / IL-15 / granzyme B / perforin / innate immunity / granzyme B / perforin / requlatory T細胞 / innate immune cells / 表面内T細胞 / IFN-γ / CD69 / fucosyltransferase VII / CLA
Research Abstract

In this study, we asked whether intraepidermal T cells abundantly detected in the resting lesions of fixed drug eruption could display phenotypic properties and functions analogous to innate immune cells, such as NK cells. We found that these T cells were composed of a phenotypically homogeneous population that expresses TCRαβ, CD3, CD8, CD45RA, CD11b, but not CD27 and CD56. This phenotype most closely resembled that of effector memory T cells. Upon stimulation with the causative drug in situ, NKG2D and CD57, frequently expressed on NK cells, were induced to be expressed on some of these intraepidermal T cells. In situ PCR study demonstrated a strong and exclusive induction of IFN-γ mRNA and protein in these T cells with much faster kinetics than their dermal and blood counterparts, upon stimulation in situ. These T cells were also found to have the capacity to kill surrounding keratinocytes through the release of cytotoxic granules, perforin and granzyme B. Thus, these T cells originally evolved to protect tissue integrity can exert an opposite action that is deleterious to the host, when activated in an enhanced or uncontrolled fashion. The activity of these potentially dangerous T cells is therefore carefully controlled to prevent unwanted tissue injury under physiological conditions.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Inoue, Y. et al.: "Inhibitory activity of CX-659S, a novel diaminauracil derivative, against the rebord phenomenon following with draual of corticosteroid therapy for chronic contact hypersensitivity resporces"Int Arch Allergy Immunol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Teraki, Y. et al.: "Preferential expression of αEβ7 integrin (CD103) on CD8^+ T cells in the psoriatic epidermis : Regulation by interleukins 4 and 12 and transforming growth factor-β"Br J Dermatol. 147. 1118-1126 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizukawa, Y. et al.: "Direct Evidence for IFN-γProduction by Effector-Memory-Type Intraepidermal T Cells Residing at an Effector Site of Immunopathology in Fixed Drug Eruption"Am J Pathol.. 161. 1337-1347 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiohara, T. et al.: "Pathophysiology of fixed drug eruption : the role of skin resident T cells"Curr Opin Allergy Clin Immunol. 2. 317-323 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Teraki, Y. et al.: "Skin-Homing Interleukin-4 and -13-Producing Cells Contribute to Bullous Pemphigoid : Remission of Disease is Associated with Increased Frequency of IL-10-Producing Cells"J Invest Dermatol. 117. 1097-1102 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizukawa, Y. et al.: "Development and Characterization of a Monoclonal Antibody Specific for Fucosyltransferase VII (Fuc-TVII). Discordant Expression of CLA and Fuc-TVII in Peripheral CD4^+ and CD8^+ T Cells"J Invest Dermatol. 117. 743-747 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiohara, T. et al.: "Lichen planus and lichenoid eruption in Dermatology"Elsevier Science(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue Y., Isobe M., Shiohara T., Hayashi H.: "Inhibitory activity of CX-659S, a novel diaminouracil derivative, against the rebond phenomenon following with drawal of corticosteroid therapy for chronic contact hypersensitivity responses"Int Arch Allergy Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Teraki Y., Shiohara T.: "Preferential expression of α_Eβ_7 intergrin (CD103) on CD^<8+> T cells in the psoriatic epidermis: regulation by interleukins 4 and 12 transforming growth factor-β"Br J Dermatol. 147. 1118-1126 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue Y., Isobe M., Shiohara T., Goto Y., Hayashi H.: "Protective and curative effects of topically applied CX-659S, a novel diaminouracil derivative, on chronic picryl chloride-induced contact hypersensitivity responses"Br J Dermatol. 147. 675-682 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizukawa Y., Yamazaki Y., Teraki Y., Hayakawa J., Hayakawa K., Nuriya H., Kohara M., Shiohara T.: "Direct evidence for IFN-γ production by effector-memory type intraepidermal T cells residing at an effector site of immunopathology in fixed drug eruption"Am J Pathol. 161. 1337-1347 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiohara T., Mizukawa Y., Teraki Y.: "Pathophysiology of fixed drug eruption: the role of skin resident T cells"Curr Opin Allergy Clin Immunol. 2. 317-323 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Teraki Y., Hotta T., Shiohara T.: "Skin-homing interleukin-4 and -13-producing cells contribute to bullous pemphigoid: remission of disease is associated with increased frequency of interleukin-10-producing cells"J Invest Dermatol. 117. 1097-1102 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizukawa Y., Shitara K., Yamazaki Y., Teraki Y., Takahashi R., Narimatsu H., Shiohara T.: "Development and characterization of a monoclonal antibody specific for fucosyltransferase VII (Fuct VII): Discordant expression of CLA and Fuc-T VII in peripheral CD4+ and CD8+ T cells"J Invest Dermatol. 117. 743-747 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiohara T., Mizukawa Y., Teraki Y., Fukuda T.: "Gamma-delta T cells with emphasis on their functional role in the epidermis"Chem Immunol. 79. 66-86 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizukawa Y., Shitara K., Yamazaki Y., Kudo A., Narimatsu H., Shiohara T.: "Immunohistochemical detection of skin-homing T cells expressing fucosyltransferase VII (Fuc-T VII) in vitro and in situ"Lab Invest. 81. 771-773 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizukawa Y., Shiohara T.: "The cytokine profile in a transient variant of angioedema with eosinophilia"Br J Dermatol. 144. 169-174 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiohara T ., Kano Y., eds. by: Bolognia J., Jorizzo JL., Rapini RP: "Chapter 012. Lichen planus and lichenoid eruption"Dermatology. Elsevier Scinence, (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiohara T., eds. by: Vohr H-W: "Springer-Verlag GmbH & Co. Berlin"Encyclopedic reference of Immunotoxicology, (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiohara, T. et al.: "Recall phenomenon : some skin-resident cells remember previous insults"Dermatology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Teraki, Y. et al.: "Perferential expression of αEβ7 integrin(CD103) on CD8^+ T cells in the psoriatic epidermis : regulation by IL 4 and 12 and transforming growth factor-β"Br J Dermatol. 147・6. 1118-1126 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizukawa, Y. et al.: "Direct evidence for IFN-γ production by effector-memory-type intraepidermal T cells residing at an effector eite of immunopathology in fixed drug eruption"Am J Pathol. 161・4. 1337-1347 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue, Y. et al.: "Protective and curative effects of topically applied CX-659S, a novel diaminouracil derivative, on chronic picryl chloride-induced contact hypersensitivity responses"Br J Dermatol. 147・4. 675-682 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiohara, T. et al.: "Dermatology"Elsevier Science(in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiohara, T. et al.: "Pathophysiology of fixed drug eruption : the role of skin resident T cells"Curr Opin in Allergy and Immunol. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Shiohara, T. et al.: "Fixed drug eruption : easily overlooked but need a new respect"Dermatology. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Mizukawa, Y. et al.: "Development and characterization of a monoclonal antibody specific for fucosyltransferase VII(Fuc-TVII):discordant expression of CLA and Fuc-TVII in peripheral CD^<4+>and CD^<8+>T cells"J Invest Dermatol. 117. 743-747 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mizukawa, Y. et al.: "Immunohistochemical detection of skin-homing T cells expressing fucosyltransferase VII (Fuc-TVII) in vitro and in situ"Lab Invest. 81. 771-773 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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