ROLE OF CD4+ TH1 LYMPHOCYTES IN PROTECTION AGAINST EIAV

描述：（改编自申请人的摘要）免疫的鉴定 似乎可以帮助控制马传染性贫血病毒（EIAV）的反应 很重要，因为类似的机制可能适用于其他慢病毒 感染。假设免疫反应参与的原因 可以根据对 EIAV 的最终控制来确定对 EIAV 的保护 马的疾病以及淋巴细胞反应的证明 负责控制。初始血浆病毒血症减少至 受感染的马匹中检测不到的水平与出现 CD8 细胞毒性 T 淋巴细胞 (CTL)，而中和抗体通常是 直到血浆病毒血症清除后才可检测到。要求为 Th1 亚群的病原体特异性 CD4 辅助 T 淋巴细胞 (HTL) 活性，如 由细胞因子的产生决定，有效的 CTL 反应是很好的 记录在案。此外，还有针对不同病毒系统的研究表明 证明仅使用可引发强 CD4 的 HTL 表位的功效 Th1 反应可增强随后的增殖和 CTL 活性 病毒挑战。这种慢病毒疫苗的方法可能会克服 鉴定通用 CTL 和 HTL 表位的困难 由广泛的主要组织相容性复合物 I 类或 I 类呈现 分别为II分子。这是因为有证据表明 这种通用HTL表位可能比通用CTL表位更常见。 此外，HTL表位位于慢病毒的保守区域 可能规避抗原变异的另一个关键问题。我们的 长期研究目标是确定HTL和CTL在控制中的作用 慢病毒感染，为了实现这一目标，我们特别需要更多 了解 CD4 T 淋巴细胞对这种免疫的贡献。对此 最后，本提案中概述的实验将直接测试 假设诱导 CD4 Th1 淋巴细胞对普遍和 保守的 EIAV 表位将促进增强的 CTL 反应，并提供 防止随后的 EIAV 挑战。

DESCRIPTION: (Adapted from Applicant's Abstract) Identification of immune responses that can help control equine infectious anemia virus (EIAV) seems important because similar mechanisms may be applicable to other lentivirus infections. Reasons for assuming that immunological responses involved in protection against EIAV can be identified are based on eventual control of the disease in horses and on the demonstration that lymphocyte responses are responsible for the control. The decrease of initial plasma viremia to undetectable levels in infected horses is associated with the appearance of CD8+ cytotoxic T lymphocytes (CTL), while neutralizing antibody often is undetectable until after clearance of the plasma viremia. The requirement for pathogen-specific CD4+ helper T lymphocyte (HTL) activity of the Th1 subset, as determined by cytokine production, for effective CTL responses is well documented. In addition, there are studies in different viral systems that demonstrate the efficacy of using only HTL epitopes that elicit a strong CD4+ Th1 response to enhance both proliferative and CTL activity upon subsequent virus challenge. Such an approach for lentivirus vaccines might overcome the difficulty of identifying both universal CTL and HTL epitopes which are presented by a broad range of major histocompatibility complex class I or class II molecules, respectively. This is because there is evidence indicating that such universal HTL epitopes may be more common than universal CTL epitopes. Further, HTL epitopes have been located in conserved regions of lentiviruses possibly circumventing another key problem of antigenic variation. Our long-term research goal is to determine the roles of HTL and CTL in the control of lentiviral infections and to achieve this goal we particularly need more knowledge of the contribution of CD4+ T lymphocytes to this immunity. To that end, the experiments outlined in this proposal will directly test the hypothesis that induction of CD4+ Th1 lymphocyte responses to universal and conserved EIAV epitopes will promote enhanced CTL responses to, and afford protection against, subsequent EIAV challenge.