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Studies on newly synthesized peptide as an immunoregulator against protozoan infection

新合成肽作为抗原虫感染免疫调节剂的研究

基本信息

批准号：
06556053
负责人：
SUZUKI Naoyoshi
金额：
$ 10.05万
依托单位：
Kitasato University, School of Veterinary Medicine, Towada (1996)Obihiro University of Agriculture and Veterinary Medicine (1994-1995)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

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 … More 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

本文研究了从细胞因子(淋巴因子)中分离出的免疫调节活性单位的新合成肽(Obiactin-Obiopepts)对弓形虫慢性感染动物的作用。用环磷酰胺(Cyp)、Obio-1(Obio-1)和/或抗CD4单抗治疗慢性感染弓形虫的小鼠，以确定这些免疫抑制剂对脑囊肿的影响。在未治疗和感染Cyp-OBI-1处理的小鼠脑内，用苏木精-伊红染色或抗弓形虫ABC染色，大多数可见大的、典型的圆形组织囊肿，在本实验研究的部分区域也可见分裂的微囊。相比之下，仅使用Cyp或用抗CD4药物治疗的感染小鼠的脑组织在某些脑区有多个大小不一的退化囊，以及成簇的微囊，然而，这种变化在用抗CD4药物治疗的小鼠中更为显著。InFEC…更多接受Cyp和OBI-1联合治疗的TED小鼠显示出80%的存活率显著高于单独使用Cyp的小鼠20%的存活率。与仅使用抗CD4抗体或仅使用Cyp的小鼠相比，联合使用Obio-1和抗-CD4或Obio-1和Cyp的小鼠的中性粒细胞、单核细胞和淋巴细胞的百分比更高。与WISE一样，Cyp和Obio-1联合治疗后，中性粒细胞和淋巴细胞计数的增加可能有助于诱导小鼠对弓形虫感染的抵抗力。这些结果表明，慢性感染弓形虫的Cyp对小鼠组织囊破裂的再激活可能主要是由CD4阳性细胞介导的，而不是由其他CD8和CD5细胞介导的。在本研究中，TLA可诱导动物体内自然杀伤(NK)细胞、细胞毒性T淋巴细胞(CTL)和淋巴因子激活的杀伤(LAK)细胞数量增加。这些杀伤细胞在动物体内的诱导需要与体内的巨噬细胞和淋巴细胞结合存在。在TLA中分离到一个活性单位为TLA-IG8，在体内和体外实验中对各种杀伤细胞的诱导作用明显强于其他细胞。利用TLA-IG8单抗，现已明确了IG8的结构。较少