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Abnormal polarization of CD4^+ T cell subsets in autoimmune-Prone New Zealand mice.

Research Project

Project/Area Number 07670383
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionTOIN UNIVERSITY OF YOKOHAMA TOIN HUMAN SCIENCE AND TECHNOLOGY CENTER

Principal Investigator

NISHIMURA Hiroyuki  TOIN KHUMAN SCINCE AND TECHNOLOGY CENTER TOIN UNIVERSITY OF YOKOHAMA PROFESSOR, 工学部・材料工学科, 教授 (60189313)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsSLE / CD4^+ T cells / activated T cells / NZB mice / (NZB*NZW) F1 mice / Th1 / Th2 / CD69 / 活性化 / 自己免疫疾患 / 全身性エリテマトーデス / New Zealand マウス / (NZB×NZW)F1
Research Abstract

Abnormal polarization of CD4^+ T cell subsets in autoimmune-Prone New Zealand mice.
High frequencies of CD4^+ T cells bearing activation antigens such as HLA-DR and -DP in blood of patients with systemic lupus erythematosus (SLE) suggest that a continuous activation of autoreactive CD4^+ T cells occurs in this disease condition. In the present stidies, we analyzed spontaneously activated CD4^+ T cells in spleens of SLE-Prone NZB and (NZB*NZW) F1 mice, using two distinct early T cell activation markers, CD69 and NTA204. A marked age-associated increase in the proportion of each CD69^+ and NTA204^+ activated CD4^+ T cells was observed in NZB and (NZB*NZW) F1, but not in non-autoimmune NZW and BALB/c mice. Interestingly, there were phenotypically separate, three types of activated T cells ; one with CD69 alone, one with NTA204, and one with both CD69 and NTA204, Studies of T cell receptor (TCR) V bata repertoire showed that these activated T cells had no skewed TCR V beta repertoire usages. Murine CD4^+ T cells could be subdivided into 4 distinct subsets, either positive or negative for CD62L (L-selectin) and NTA260, an antigendefined by a hybridoma monoclonal autoantibody from autoimmune NZB mice. It was found that all three activated CD4^+ T cell subpopulations were included in the CD62L-NTA260-CD4^+ T cell subset. This subset was unique because it belonged to neither naive nor memory CD4^+ T cells. It also did not functioon as either Th1 or Th2, based on its cytokine production patterns. As such CD62L-NTA260-CD4^+ T cell subset became the major population of CD4^+ T cells in aged NZB and (NZB*NZW) F1 mice, further phenotypical and functional analysis of this subset may provide insightsinto the mechanisms of the generation of autoreactive T cells responsible for the pathogenesis of SLE.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(11 results)

All Other

All Publications

  • [Publications] Nishimura H,et al.: "Functional CD4+ T cell subsets defined by expression of CD45RC and NTA260 antigens and age-associated polarization in murine lupus." Internat. Immunol.7. 1,115-1,123 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tokushige K.et al.: "Abnormal T cell activation and skewed T cell receptor V beta repertoire usage in Japanese Patients with Idiopathic Portal Hypertension:" Clin. Immunol. Immunopathol.75. 203-213 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishimura H.et al.: "Effects of transgenic mixed-haplotype MHC class II molecules AadAbz on autoimmune disease in New Zealand mice." Internat. Immunol.8. 7-976 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤倉 新、西村裕之、他: "全身性エリテマトーデス(SLE)モデルに発見された新しい早期活性化CD4^+T細胞亜集団" 順天堂医学. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishimura H,Hattori S,Ueda G.Abe M,Yang K,Nozawa S,Okamoto H,Zhang D,Tsurui H,Hirose S and Shirai T: "Functional CD4^+ T cell subsets defined by expression of CD45RC and NTA260 antigens and age-associated polarization in murine lupus." Internat, Immunol. 7. 1115-1123 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tokushige K,Hirose S,Nishimura H,Fujimori M,Yamauchi K,Obata H,Futagawa S and Shirai T: "Abnormal T cell activation and skewed T cell receptor V bata repertoire usage in Japanise patients with Idiopathic Portal Hypertension" Clin.Immunol, Immunopathol. 75. 203-213 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishimura H,Ishikawa S,Nozawa S,Awaji M,Saito J,Abe M and Shirai T: "Effects of transgenic mixed-haplotype MHC class II molecules AadAbz on autoimmune disease in New Zealand mice." Internat.Immunol. 8. 967-976 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiroyuki Nishimura 他: "Effects of transgenic mixed-haplotype MHC class II molecules Aα^dAβ^z on autoimmune diseases in New Zealand mice." International Immunology. 8. 967-976 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 赤倉新、西村裕之他: "全身性エリテマトーデス(SLE)モデルに発見された新しい早期活性化CD^+T細胞亜集団" 順天堂医学. (発表予定). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishimura H, et al.: "Functional CD4+ T cell subsets defined by expression of CD45RC and NTA260 antigens and age-associated polarization in murine lupus." Int. Immunol.7:. 1115-1123 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tokushige K. et al.: "Abnormal T cell activation and skewed T cell receptor Vbeta repertoire usage in Japanese Patients with Idiopathic Portal Hypertension:" Clin. Immunol. Immunopathol.75:. 206-213 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-03-31   Modified: 2016-04-21  

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