| Project/Area Number |
13670259
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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 |
寄生虫学(含医用動物学)
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
ASAHI Hiroko National Institute of Infectious Diseases, Department of Parasitology, Senior Researcher, 主任研究官 (90231109)
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| Co-Investigator(Kenkyū-buntansha) |
KANAZAWA Tamotsu University of Occupational and Environmental Health, Department of Parasitology and Tropical Medicine, Professor, 医学部, 教授 (10194888)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Schistosoma / egg components / granuloma formation / helper T lymphocyte / egg-induced immunopathology / Schistosoma / 虫卵抗原 / 遺伝子クローニング / Sm-p25 / サイトカイン産生 / 抗体産生 / Sm-prealbumin / Sm-GST / IL-4 inducing / thioredoxin peroxidase / レコンビナント蛋白 |
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| Research Abstract |
In schistosomiasis, granuloma formation to parasite eggs signals the beginning of a chronic and potentially life-threatening disease. Granulornas are strictly mediated by CD4^+ T helper (Th) cells specific for egg antigens ; however, the number and identity of these T cell-sensitizing molecules are largely unknown. We have used monoclonal T cell reagents as probes to track down, isolate and positively identify several egg antigens ; this approach implicitly assures that the molecules of interest are T cell immunogens and, hence, potentially pathogenic. The best-studied egg component is the Sm-p40 antigen. Sm-p40 elicits a strikingly immunodominant Th-1-polarized response in C3H and CBA mice, which are characterized by severe egg-induced immunopathology. Two additional described T cell-sensitizing egg antigens are Schistosoma mansoni phosphoenolpyruvate carboxykinase (Sm-PEPCK) and thioredoxin peroxidase-1 (Sm-TPx-1). In contrast to Sm-p40,both of these molecules induce a more balanced Th-1/Th-2 response, and are relatively stronger antigens in C57BL/6 mice, which develop smaller egg granulomas. Other components, including moieties with molecular weights of 25 kDa (Sm-p25),150/166kDa (Sm-p155/166), and 29 kDa (Sm-GST29), are also found to stimulate specific T cells. These findings in the murine model introduce the important notion that egg antigens can vary significantly in immunogenicity according to the host's genetic background. A better knowledge of the principal immunogenic egg components is necessary to ascertain whether such responses can be manipulated for the purpose of reducing pathology.
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