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

免疫调节剂，如TLA（弓形虫裂解抗原）在实验中进行了测试。肌内注射TLA可抑制20-甲基胆蒽（MC）在大鼠和小鼠体内自诱导的肿瘤生长。TLA的抗肿瘤活性在肿瘤生长早期最为明显。大鼠在肿瘤出现前给予TLA，肿瘤形成略有延迟。用抗Thy-1抗体对肿瘤组织进行免疫组织学检查，经TLA处理的大鼠肿瘤组织中有大量的Thy-1阳性或淋巴因子活化杀伤细胞（LAK），而未经TLA处理的大鼠肿瘤组织中只有少量的Thy-1阳性或NK细胞。在这一系列的研究中，TLA在动物体内注射后诱导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。目前从TLA中分离出一个活性单元为TLA- h6e，与其他活性单元相比，其对TLA- h6e的抑制活性明显较强。利用TLA-H6E单克隆抗体，H6E的结构现已清晰。研究了从细胞因子（淋巴因子）中分离出的活性单元新合成的肽对慢性弓形虫感染动物的影响。用氯磷酰胺（Cyp）、Obio-1 （Obio-1）和/或抗cd4单克隆抗体治疗慢性弓形虫感染小鼠，以测定这些免疫抑制剂对脑内囊肿的影响。在未处理和感染Cyp-Obi-1处理的小鼠大脑中，通过HE染色或抗弓形虫ABC标记染色，大多检测到典型的大圆形组织囊肿，在某些区域还发现分裂的微囊肿。相比之下，仅Cyp或抗cd4处理的感染小鼠脑组织在某些脑区出现多个大小不等的变性囊肿，以及簇状微囊肿，但这种变化在抗cd4处理的小鼠中更为明显。用Cyp和Obi-1联合治疗的感染小鼠的存活率为80%，明显高于只用Cyp治疗的小鼠的20%存活率。与仅使用抗cd4抗体或仅使用Cyp的小鼠相比，使用Obi-1和抗cd4或Obi-1和Cyp联合治疗的小鼠中中性粒细胞、单核细胞和淋巴细胞的百分比更高。在Cyp和Obi-1联合治疗后，嗜中性白细胞和淋巴细胞计数的增加可能同样有助于诱导小鼠对刚地弓形虫的抗性。这些结果表明，慢性弓形虫感染小鼠经Cyp处理后，组织囊肿破裂的再激活可能主要由CD4阳性细胞介导，而非其他CD8、CD5细胞。此外，Obi-1和Cyp联合治疗后，嗜中性白细胞的增加可能有助于诱导小鼠对弓形虫的抗性。然而，这些结果似乎表明，慢性弓形虫感染小鼠的组织囊肿的再激活或破裂与Cyp治疗小鼠的死亡并不主要相关。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