Project/Area Number |
06556053
|
Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 試験 |
Research Field |
Applied veterinary science
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Research Institution | Kitasato University, School of Veterinary Medicine, Towada (1996) Obihiro University of Agriculture and Veterinary Medicine (1994-1995) |
Principal Investigator |
SUZUKI Naoyoshi Prof., Kitasato Univ., Sch.Vet.Med., 獣畜学部, 教授 (10003071)
|
Co-Investigator(Kenkyū-buntansha) |
OMATA Yoshitaka Assoc.Prof., Obihiro U., Sch.Vet.Med., 畜産学部, 助教授 (10132987)
IGARASHI Ikuo Assoc.Prof., Obihiro U., Res.Ctr.Proto., 原虫病分子免疫研究センター, 助教授 (80159582)
NAGASAWA Hideyuki Prof., Obihiro Univ., Res.Ctr.Protooz., 原虫病分子免疫研究センター, 教授 (60172524)
SAITO Atsushi Prof., Obihiro Univ., Sch.Vet.Med., 畜産学部, 教授 (10002263)
TOYODA Yutaka Prof., Obihiro Univ., Res.Ctr.Protooz., 原虫病分子免疫研究センター, 教授 (90050418)
佐藤 基佳 帯広畜産大学, 畜産学部, 助教授 (50003140)
広瀬 恒夫 帯広畜産大学, 畜産学部, 教授 (60003076)
|
Project Period (FY) |
1994 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 1996: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1995: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1994: ¥8,000,000 (Direct Cost: ¥8,000,000)
|
Keywords | Toxoplasma / Animals / Obiopeptides / Immmunoregulator / Cyclophosphamide / Immunomodulator / TLA / Lymphocytes / Macrophages / Neospora caninum / Toxoplasma gondii / 感染防御 / ワクチン / マウス / 合成ペプチド / 感染抵抗性 |
Research Abstract |
Newly synthesized peptide (Obioactin to Obiopeptides) of the activity units which were isolated from cytokines (lymphokines) as an immunoregulator were examined in the effect of Toxoplasma chronically infected animals. Mice chronically infected with Toxoplasma gondii were treated with cyclophosphamide (Cyp), Obiopeptide-1 (Obio-1) and/or anti-CD4 monoclonal antibody to determine the effect of these immunosuppressive agents on the cysts in the brain. In the brain of non-treated, and infected Cyp-Obi-1 treated mice, with hematoxyline-eosine staining or anti-Toxoplasma ABC lebelling staining, large typicallly rounded tissue cysts were mostly detected, and in some regioins dividing microcysts were also observed in this experimental sutdies. In contrast, brain tissue from Cyp only or anti-CD4 treated infected mice had multiple degenerated cysts of varied sizes in some brain regions, as well as clusters of microcysts, however, such change was more striking in the anti-CD4 treated mice. Infec
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ted mice treated with a combination of Cyp and Obi-1 showed a significantly higher survival of 80% compared to 20% survival in mice treated with Cyp only. Percent neutrophilic leucocytes, monocytes and lymphocytes in mice treated with a combination of Obio-1 and anti-CD4, or Obio-1 and Cyp were higher compared to those groups treated with anti-CD4 antibody, or Cyp only. The increase in neutrophilic leucocyte and lymphocyte counts after a combined Cyp and Obio-1 treatment may, like wise, contribute to the induction of resistance in mice against Toxoplasma gondii infection. These results indicate that reactivation of rupture of tissue cysts in mice treated with Cyp, chronically infected with Toxoplasma, mignt be mainly mediated by CD4 positive cells rather than other CD8 and CD5 cells. An immunoregulator or immunomodulator, such as Toxoplasma lysate antigen (TLA) was tested in our studies. In this studies, TLA induces in numbers of natural killer (NK) cells, cytotoxic T-lymphocytes (CTL) and lymphokine-activaed killer (LAK) cells in animals after TLA injection. The induction of these killer cells in animal bodies needs to exist in combination with macrophages and lymphocytes in their in vivo. An acitivity unit in TLA was isolated as TLA-Ig8, and the induction of the various killer cells in vivo and in vitro tests was significantly strong in comparison with others. Using the TLA-Ig8 monoclonal antibody, the structure of Ig8 is now making clear. Less
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