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Autoreactive V alpha 14 T cell and their contribution of the development of autoimmune diseases

Research Project

Project/Area Number 04452298
Research Category

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

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionChiba University

Principal Investigator

TANIGUCHI Masaru  Chiba University, School of Medicine, Professor, 医学部, 教授 (80110310)

Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1993: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1992: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsInvariant TCR / Valpha14 T cell / Extrathymic development / Double negative T cell / Autoimmunity / Autoreactive T cell / Peripheral tolerance
Research Abstract

We found that a homogenous CD4-/CD8- T cell bearing invariant TCR encoded by Valpha14Jalpha281 with a one-base N-region is highly dominated in the periphery (2-3% in spleen). Surprisingly the high expression of the homogenous Valpha14 TCR is a general phenomenon in all laboratory strains irrespective of MHC haplotypes and in some wild mouse subspecies. The majority of Valpha14^+ TCR are associated with Jalpha other than Jalpha281 at the neonatal stage and then the frequency of invariant Valpha14Jalpha281 TCR expression increases with time and reached a maximum at around 5-8 weeks after birth. The dominant expression of Valpha14Jalpha281 TCR is found both in euthymic and athymic mice.
These results indicate that homogenous Valpha14Jalpha281 T cells are positively selected in the periphery without thymic influence and that their VJ junction is important for the positive selection. We also demonstrate that Valpha14^+ TCR gene rearrangements take place in extrathymic sites, such as bone marrow, liver, and intestine, since frequent nonproductive Valpha14 TCR products and Valpha14-Jalpha281 gene mediated signal sequences of the circular DNA are detected as a result of TCR rearrangements in extrathymic tissues rather than the thymus, indicating the extrathymic development of Valpha14Jalpha281 T cells. No circular DNA generated by Valpha1.1-Jalpha281 which is known to be thymus-dependent was detected in extrathymic tissues of athymic mice. Moreover, the decrease in the invariant Valpha14 TCR expression was tightly correlated with the development of autoimmune diseases. This suggests the crucial role of the invariant Valpha14Jalpha281 T cells in the regulation of anti-self responses.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yasuhiko MAKINO: "Extrathymic differentiation of a T cell bearing invariant VαJα281 TCR" Intern.Rev.Immunol.(In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Beate C.SYDORA: "Intestinal intraepithelial lymphocytes preferentially home to the intestinal epithelium" Intl.Immunol.5. 743-751 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Haruhiko KOSEKI: "V-alpha-14 T-cell antigen receptor repertoire and its function" Intl.Arch.Allergy and Immunol.99. 416-418 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yasuhiko MAKINO: "Extrathymic development of Vα14 positive T cells" J.Exp.Med.177. 1399-1408 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Toshihiro ITO: "Monoclonal antibody against murine T cell receptor Vα14 cross-reacts with human CD3-ε and detects disulfied-linked dimeric form" Intl.Immunol.3. 991-995 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Rieko KANNO: "Genetics in Wild Mice:Its application to biomedical research" Kazuo MORIWAKI,Toshio SHIROISHI,Hiromichi YONEKAWA(In press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Makino, Y., Koseki, H., Adach, Y., Akasaka, T., Tsuchida, K., and Taniguchi, M.: "Extrathymic differentiation of a T cell bearing invariant Valpha14 Jalpha281 TCR" Intern. Rev.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sydora, B.C., Habu, S.and Taniguchi, M.: "Intestinal intraepithelial lymphocytes preferentially home to the intestinal epithelium" Intl.Immuno.5. 743-751 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Koseki, H., Makino, Y., Adachi, Y.and Taniguchi, M.: "V-alpha-14 T-cell antigen receptor repertoire and its function" Intl.Arch.Allergy and Immunol.99. 416-418 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Makino, Y., Yamagata, N., Sasho, T., Adachi, Y., Kanno, R., Koseki, H., Kanno, M and Taniguchi, M.: "Extrathymic development of Valpha14 positive T cells" J.Exp.Med.177. 1399-1408 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ito, T., Ishibashi, K., Imai, K., Koseki, H., Kantake, M., Ra, C., Fernandez, E., Saito, T.and Taniguchi, M.: "Monoclonal antibody against murine T cell receptor Valpha14 cross-reacts with human CD3-epsilon and detects disulfied-linked dimeric form" Intl.Immunol.3. 991-995 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yasuhiko MAKINO: "Extrathymic differentiation of a T cell bearing invariant VαJα281 TCR" Intern.Rev.Immunol.(In press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Beate C.SYDORA: "Intestinal intraepithelial lymphocytes preferentially home to the intestinal epithelium" Intl.Immunol.5. 743-751 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Haruhiko KOSEKI: "V-alpha-14 T-cell antigen receptor repertoire and its function" Intl.Arch.Allergy and Immunol.99. 416-418 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yasuhiko MAKINO: "Extrathymic development of Vα14 positive T cells" J.Exp.Med.177. 1399-1408 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Toshihiro ITO: "Monoclonal antibody against murine T cell receptor Vα14 cross-reacts with human CD3-ε and detects disulfied-linked dimeric form" Intl.Immunol.3. 991-995 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Rieko KANNO: "Genetics in Wild Mice:Its application to biomedical research" Kazuo MORIWAKI,Toshio SHIROISHI,Hiromichi YONEKAWA, (In press)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masahiko SUZUKI: "Expansion of murine T cells bearing a unique TCR β-chain in Friend virus-induced tumor in situ" J.Immunol. 148. 2968-2973 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hideki HAYASHI: "Molecular cloning and characterization of the gene encoding mouse melanoma antigen by cDAN library transfection" J.Immunol. 149. 1223-1229 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takuji SHIRASAWA: "Heavy chain variable (V_H) region diversity generated by V_H gene replacement in the proginy of a single precursor cell transformed with a temperature-sensitive mutant of abelson murine leukemia virus" J.Exp.Med.176. 1209-1214 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yasuhiko MAKINO: "Extrathymic development of Vα14 positive T cells" J.Exp.Med.

    • Related Report
      1992 Annual Research Report
  • [Publications] Haruhiko KOSEKI: "Vα14 TCR repertoire and its function" Intl.Arch.Allergy and lmmunol.

    • Related Report
      1992 Annual Research Report
  • [Publications] Takayuki SUMIDA: "Basic studies on germ-line transmission of ES-derived genes.In:Molecular approaches to the study and treatment of human deseases" ed.by Yoshida,T.O.and wilson,J.M.J.M.Exderpta Medica.Amsterdam, 455 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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