Abnormal polarization of CD4^+ T cell subsets in autoimmune-Prone New Zealand mice.
| Project/Area Number | 07670383 |
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | TOIN UNIVERSITY OF YOKOHAMA TOIN HUMAN SCIENCE AND TECHNOLOGY CENTER |
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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)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed(Fiscal Year 1996)
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| 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)
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| Keywords | SLE / 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 |
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| 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.
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Report
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Research Products
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