IMMUNE CONTROL OF EQUINE INFECTIOUS ANEMIA LENTIVIRUS

这项拟议研究的总体目标是描绘出免疫 可以控制慢病毒感染的机制。慢病毒系统 需要研究的是马身上的EIAV，它会导致病毒血症的发作 在发热、贫血、血小板减少和肝脏淋巴细胞病变中 和其他器官。大多数马会终止最初的病毒血症和复发 最终成为病毒水平很低的无症状携带者。 表明淋巴细胞反应控制EIAV的数据包括观察 患有遗传性严重联合免疫缺陷的小马驹 不能控制EIAV感染后的初始病毒血症，与之相反 正常小马驹和皮质类固醇治疗EIAV携带者诱导 病毒血症和疾病。EIAV的免疫控制将通过检测进行解剖 CD8+细胞毒性T淋巴细胞(CTL)控制EIAV和 受感染马匹中的疾病。即使有效的疫苗很可能 诱导几种重要的保护性免疫功能，这是 目前的知识是了解慢病毒在体内的作用- 特异性MHC限制性CD8+CTL在控制感染中的作用我们的 MHC限制性CD8+CTL对Env和GAG/PR蛋白的抑制作用 感染EIAV的马未经刺激的PBMC表位提供了一种 获得关于其在控制中的作用的明确信息的机会 这种慢病毒感染。这样的数据可能适用于其他慢病毒 包括HIV-1，对CTL在体内的作用的剖析更多 很难。使用感染EIAV的马的CD8+CTL将有助于 病毒识别的免疫优势表位的鉴定 用于诱导所需CTL的对照。最后，关于 CD8+CTL在体内的作用可以通过挑战进一步评估 这些用同源和异种EIAV免疫的马，通过 确定CD8+T淋巴细胞耗尽是否会阻止终止 感染的马出现初始病毒血症。

The overall goal of the proposed research is to delineate immune mechanisms that can control lentiviral infections. The lentiviral system to be studied is EIAV in horses which has episodes of viremia resulting in fever, anemia, thrombocytopenia and lymphocytic lesions in the liver and other organs. Most horses terminate initial viremia and recurrences to eventually become asymptomatic carriers with very low levels of virus. Data indicating lymphocyte responses control EIAV include the observation that foals with genetically based severe combined immunodeficiency can not control the initial viremia following EIAV infection, in contrast to normal foals, and corticosteroid treatment of EIAV in carriers induces viremia and disease. Immune control of EIAV will be dissected by testing the assumption that CD8+ cytotoxic T lymphocytes (CTL) control EIAV and disease in infected horses. Even though effective vaccines will likely induce several important protective immune functions, a major gap in current knowledge is understanding the in vivo role of lentiviral- specific MHC-restricted CD8+ CTL in controlling infections. Our demonstration of MHC-restricted CD8+ CTL to Env and Gag/PR protein epitopes in unstimulated PBMC from EIAV infected horses provides an opportunity to obtain definitive information on their role in controlling this lentiviral infection. Such data may apply to other lentiviruses including HIV-1 where dissection of the in vivo role of CTL is more difficult. Use of CD8+ CTL from EIAV infected horses will facilitate identification of the immunodominant epitopes recognized during virus control for use in inducing the desired CTL. Finally, questions about the in vivo role of CD8+ CTL can be further evaluated by challenging these immunized horses with homologous and heterologous EIAV, and by determining if CD8+ T lymphocyte depletion will prevent termination of initial viremia in infected horses.