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2004 Fiscal Year Final Research Report Summary

Analysis of mechanisms by which CD8^+ T cells differentiate into the skin-homing phenotype

Research Project

Project/Area Number 15390344
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, Department of Dermatology, Professor, 医学部, 教授 (10118953)

Co-Investigator(Kenkyū-buntansha) TERAKI Yuichi  Kyorin University, School of Medicine, Department of Dermatology, Assistant Professor, 医学部, 講師 (10188667)
MIZUKAWA Yoshiko  Kyorin University, School of Medicine, Department of Dermatology, Instructor, 医学部, 助手 (50301479)
HAYAKAWA Jun  Kyorin University, School of Medicine, Department of Dermatology, Instructor, 医学部, 助手 (30255393)
Project Period (FY) 2003 – 2004
Keywordsskin-homing / CD8^+ T cell / E-selectin ligand / fucosyltransferase / CLA / CCR-4 / cytokine
Research Abstract

In this study, we asked how expression of two fucosyltransferases (Fuc Ts), Fuc T-IV and Fuc T-VII, can be regulated in the process of skin-homing CD8^+ T cell differentiation. We demonstrated with the use of transfectants that E-selectin ligand (ESL) epitope generated by Fuc T-IV is different from that generated by Fuc T-VII ; and that Fuc T-IV generates only low. levels of ESL without CLA expression while Fuc T-VII constructs high levels of ESL with concomitant expression of CLA. Our phenotypic analysis of memory CD8^+ T cells differentiated from naive T cells under various conditions showed that the transition from the ESL^+CLA^- to the ESL^<++>CLA^+ phenotype progressively occurred in parallel with down-regulation of Fuc T-IV expression when transferred to resting culture with IL-12. In contrast, Fuc T-VII expression was down-regulated as the T cells were transferred to IL-4-rich resting culture, where Fuc T-IV remained unchanged and the ESL^<++>CLA^+ phenotype was not detected. These results indicate that under conditions where Fuc T-IV is abundantly expressed the Fuc T-VII-dependent ESL is prevented from cell surface expression ; however, once availability of the substrate, N-acetyllactosamine, is limited, Fuc T-IV is down-regulated due to competition of this substrate, thereby allowing the T cell to express the Fuc T-VII-dependent ESL epitope with high avidity to E-selectin. Thus, the dynamic balance between Fuc T-IV and Fuc T-VII depending on their state of a activation and differentiation is a major check point for the regulation of skin-homing CD8^+ T cell differentiation.

  • Research Products

    (12 results)

All 2006 2005 Other

All Journal Article (12 results)

  • [Journal Article] Drug-induced hypersensitivity symdrome (DISH) : A reaction induce by a complex interplay among herpesviruses and antiviral and antidrue immune responses.2006

    • Author(s)
      Shiohara T
    • Journal Title

      Allergol Int 55・1

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Drug-induced hypersensitivity syndrome (DIHS) : A reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses.2006

    • Author(s)
      Shiohara T, Kano Y
    • Journal Title

      Allergol Int 55(1)

      Pages: 1-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] T-cell dynamics of inflammatory skin disease.2005

    • Author(s)
      Shiohara T
    • Journal Title

      Exp Rev Clin Immunol 1・3

      Pages: 357-368

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The immunological basis of lichenoid tissue reaction.2005

    • Author(s)
      Shiohara T
    • Journal Title

      Autoimmunity Review 4・4

      Pages: 236-241

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Are viral infections responsible for the development of drug-induced hypersensitivity syndrome as well as graft-versus-host diseases?2005

    • Author(s)
      Shiohara T
    • Journal Title

      Dermatology 210・4

      Pages: 259-260

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] T-cell dynamics of inflammatory skin diseases.2005

    • Author(s)
      Shiohara T, Mizukawa Y, Takahashi R, Hayakawa J, Hayakawa K
    • Journal Title

      Exp Rev Clin Immunol 1(3)

      Pages: 357-368

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The immunological basis of lichenoid tissue reaction.2005

    • Author(s)
      Shiohara T, Mizukawa Y
    • Journal Title

      Autoimmunity Review 4(4)

      Pages: 236-241

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Are viral infections responsible for the development of drug-induced hypersensitivity syndrome as well as graft-versus-host diseases?2005

    • Author(s)
      Shiohara T, Kano Y
    • Journal Title

      Dermatology 210(4)

      Pages: 259-260

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] NK cells and γδ^+T cells are phenotypically and functionally defective due to preferential apoptosis in patients with atopic dermatitis.

    • Author(s)
      Katsuta M
    • Journal Title

      J Immunol (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hypogammaglobulinemia as an early sign of drug-induced hypersensitivity syndrome.

    • Author(s)
      Kano Y
    • Journal Title

      J Am Acad Dermatol (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] NK cells and γδ^+ T cells are phenotypically and functionally defective due to preferential apoptosis in patients with atopic dermatitis.

    • Author(s)
      Katsuta M, Takigawa Y, Kimishima M, Inaoka M, Shiohara T
    • Journal Title

      J Immunol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hypogammaglobulinemia as an early sign of drug-induced hypersensitivity syndrome.

    • Author(s)
      Kano Y, Seishima M, Shiohara T
    • Journal Title

      J Am Acad Dermatol (in press)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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