| Co-Investigator(Kenkyū-buntansha) |
三浦 弘之 帯広畜産大, 教授 (90003079)
HIROSE Tsuneo Prof., Vet.Radiology, Obihiro Univ., 獣医放射線学, 教授 (60003076)
OMATA Yoshitaka Assoc.Prof., Vet.Physiol., Obihiro Univ., 獣医生理学, 助教授 (10132987)
IGARASHI Ikuo Assoc.Prof., Res.Cent.Protozool., Obihiro Univ., 原虫免疫研, 助教授 (80159582)
SAITO Atushi Prof., Vet.Physiol., Obihiro University, 獣医生理学, 教授 (10002263)
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| Research Abstract |
Using newly synthesized peptides on the activity units which were isolated from lymphokines as an immunoregulator, Obiopeptide, the effect of immunosuppression caused by cyclophosphamide to animals cronically infected with Toxoplasma gondii was examined. Mice chronically infected with Toxoplasma, were treated with cyclophosphamide or anti-CD4 monoclonal antibody to identify the effect of these immunosuppressive reagents on the cysts in the brain of infected mice. The effect of obiopeptide as an immunomodulator treatment of the immunosuppressed mice was also analyzed. In the brain of non-treated and cyclophosphamide-treated, chronically Toxoplasma infected mice mainly typicallarge tissue cysts, and sometimes divided cysts, were detected after staining with anti-Toxoplasma ABC technique. In contrast, the brain from anti-CD4 treated, chronically infected mice, contained multiple deeneated Toxoplasma tissue cysts of different size in some partialregions in the brain. Mice chronicaly infect
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ed with Toxoplasma and treated with a combination of cyclophosphamide and obiopeptide showed a significantly higher survival rate than those treated with cyclophosphamide alone. The percentage of neutrophils and lymphocytes in mice treated with a combination of Obiopeptide and anti-CD4, or obiopeptide and cyclophosphamide, was higher than that of mice treated with anti-CD4 or cyclophosphamide alone. These results indicate that reactivaion or rupture of tissue cysts in mice treated with cyclophosphamide, chronically infected with Toxoplasma, might be mainly mediated by CD4 positive cells rather than other immunocomponent cells. The increase of neutrophilic leukocytes might contribute tothe induction of the resistance to Toxoplasma gondii in mice, after treatment with obiopeptide and cyclophosphamide in combination.
On the other hand, an immunopotentiator such as TLA (Toxoplasma Lysate Antigens) was tested in our experimental studies. Growth of the tumor autoinduced by 20-methylcholantherne (MC) in rats was inhibited after administration of TLA.The antitumor activity of TLA was most obvious in the early stage of tumoral growth. When TLA was administered to rats before the appearance of tumor, tumor formation was delayd slightly. According to the immunohistological examination of tumor tissue with anti-Thy-a antibody, the rats treated with TLA showed large Thy-1 positive or Lymphokine-Activated Killer (LAK) cells, whereas the untreated rats indicated only a few small Thy-a positive or NK cells. These observation indicate that TLA is a useful modifier of biological responses to MC-induced tumors. In a series of these studies, TLA induces NK cells, cytotoxic T-lymphocytes and LAK cells in animals after injection, however, the induction of these killer cells needs to combine with monocyte-macrophages in in vivo. Less
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