CTL Effectors in Bovine Congenital Neosporosis

描述(由申请者提供)：申请者建议学习该角色 CTL在控制新孢子虫经胎盘传播中的作用 杂交的牛宿主。感染犬新城疫杆菌的哺乳动物宿主 免疫期间感染复发和速殖子寄生虫血症 抑制或怀孕导致胎儿感染，寄生虫性脑炎， 以及通过垂直传播在某些宿主人群中持续感染 变速箱。细胞毒性T淋巴细胞(CTL S)在免疫控制中的重要作用 小鼠感染弓形虫，通过过继转移和 枯竭研究。CD8细胞毒效应分子与优势1型免疫 应答与细胞内顶端复合体感染的缓解有关。 弓形虫免疫优势表面蛋白SAG1免疫小鼠 开发可通过SAG1过继转移的保护性免疫 犬新城疫抗原感染小鼠的特异性CTL、CD8 T淋巴细胞 保护免受弓形虫的攻击，这表明保护性CTL可能 被同源抗原诱导。在新孢子增多症小鼠妊娠模型中， 与犬新城疫抗原免疫一起中和2型反应 孕前减少胎盘传播。拟议的研究 将检验这样一种假设，即识别犬新城疫杆菌抗原的免疫 通过细胞毒性淋巴细胞将限制犬新城疫杆菌在 牛群。该项目的重点是NcSAG1，这是主要的表面抗原。

DESCRIPTION (provided by applicant): The applicant proposes to study the role of CTL's in the control of transplacental Neospora caninum transmission in an outbred bovine host. Mammalian hosts infected with N. caninum experience recrudescence of infection and tachyzoite parasitemia during immune suppression or pregnancy leading to fetal infection, parasitic encephalitis, and persistence of infection within some host populations via vertical transmission. Cytotoxic T lymphocytes (CTL s) are important in immune control of murine infections with T. gondii, demonstrated by adoptive transfer and depletion studies. CD8+ cytotoxic effectors and a dominant type 1 immune response correlate with resolution of intracellular apicomplexan infections. Mice immunized with SAG1, an immunodominant surface protein of T. gondii develop protective immunity that can be adoptively transferred with SAG1 specific CTL's. CD8+ T lymphocytes from mice infected with N. caninum antigen protect against challenge with T. gondii, suggesting that protective CTLs may be induced by homologous antigens. In murine pregnancy models of neosporosis, neutralization of a type 2 response together with N. caninum antigen priming prior to gestation decrease transplacental transmission. The proposed research will test the hypothesis that immunization with N. caninum antigens recognized by cytotoxic lymphocytes will limit congential N. caninum transmission in cattle. The project focuses upon NcSAG1, the major surface antigen.