Studies on no-specifical immunoregulatory effects to the host by the addministration of newly activated-peptides derived from Toxoplasma lysate substance

实验中检测了一种免疫调节剂，如TLA(弓形虫裂解抗原)。肌肉注射TLA后，大鼠和小鼠的肿瘤生长均受到抑制，TLA的抗肿瘤活性在肿瘤生长的早期最为明显。肿瘤出现前给予TLA，肿瘤形成略有延缓。抗Thy-1抗体免疫组织学检查显示，TLA治疗组大鼠肿瘤组织中可见大量Thy-1阳性细胞或淋巴因子激活的杀伤细胞(LAK)，而未治疗组大鼠仅有少量Thy-1阳性细胞或NK细胞。在一系列研究中，TLA在注射后在动物体内诱导NK细胞、细胞毒性T淋巴细胞和LAK细胞，而这些杀伤细胞的诱导需要在体内与巨噬细胞和淋巴细胞结合存在。现已分离出Tla中的一个活性单位为Tla-H6E，并对Tu-…具有抑制活性与其他公司相比，更多的增长明显强劲。利用TLA-H6E单抗，使H6E的结构变得清晰。从细胞因子(淋巴因子)中分离出新合成的活性单位的多肽，作为免疫调节物质，观察其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单抗治疗慢性弓形虫感染的小鼠，观察这些免疫抑制剂对脑囊肿的影响。在未经治疗和感染Cyp-OBI-1的小鼠脑内，经HE染色或抗弓形虫ABC标记后，可见较大的典型圆形组织囊，部分区域也可见分隔的微囊。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。用Cyp和OBI-1联合治疗的感染小鼠的存活率明显高于仅用Cyp治疗的小鼠，存活率为80%，而单独治疗的小鼠存活率为20%。OBI-1和抗-CD4或OBI-1和Cyp联合治疗的小鼠的中性粒细胞、单核细胞和淋巴细胞的百分比高于单独使用抗CD4抗体或Cyp的小鼠。在Cyp和OBI-1联合治疗后，中性粒细胞和淋巴细胞计数的增加可能与WISE一样，有助于诱导小鼠对弓形虫的耐药性。这些结果表明，慢性感染弓形虫的Cyp感染小鼠，其组织囊破裂的再激活可能主要由CD4阳性细胞介导，而不是由其他CD8、CD5细胞介导。此外，OBI-1和Cyp联合治疗后，中性粒细胞增多可能是诱导小鼠对弓形虫产生抵抗力的原因之一。然而，这些结果似乎表明，慢性感染弓形虫的小鼠的组织囊重新激活或破裂与Cyp处理的小鼠的死亡没有主要关系。较少

An imunomodulator, such as TLA (Toxoplasma lysate antigens) was tested in the experiments. Growth of the tumor autoinduced by 20-methylcholanthrene (MC) in rats and mice was inhibited after intramuscular injection of TLA.The antitumor activity of TLA was most obvious in the early stage of tumor growth. When TLA was administered to rats before the appearance of tumor, tumor formation was delayd slightly. According to the immunohistological examination of tumor tisue with anti-Thy-1 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-1 positive or NK cells. In a series of these studies, TLA induces NK cells, cytotoxic T-lymphocytes and LAK cells in animals after injection, and the induction of these killer cells needs to exist in combination with macrophages and lymphocytes in in vivo. An activity unit in TLA was isolated now as TLA-H6E,and the inhibitory activation to the tu … More mor growth was significantly strong in comparison with others. Using the TLA-H6E monoclonal antibody, the structure of H6E is now making clear.Newly synthesized peptides of the activity units which were isolated from cytokines (lymphokines) as an immunoregulator, Obiopeptide, were examined in the effect of Toxoplasma chronically infected animals. Mice chronically infected with Toxoplasma were treated with Chclophosphamide (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 HE staining or anti-Toxoplasma ABC labelling staining, large typically rounded tissue cysts were mostly detected, and in some regions dividing microcysts were also founded. 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. Infected 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 Obi-1 and anti-CD4, or Obi-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 Obi-1 treatment may, like wise, contribute to the induction of resistance in mice aginst Toxoplasma gondii. These results indidcate that reactivation of rupture of tissue cysts in mice treated with Cyp, chronicaly infected with Toxoplasma, might be mainly mediated by CD4 positive cells rather than other CD8, CD5 cells. Furthermore, the increase of neutrophilic leukocytes might contribute to the induction of the resistnce to Toxoplamsa in mice, after treatment with Obi-1 and Cyp in combination. However, these results seem to suggest that the reactivation or rupture of tissue cysts in mice chronically infected with Toxoplasma is not principally correlated with the death of Cyp treated mice. Less