ROLE OF CD4+ TH1 LYMPHOCYTES IN PROTECTION AGAINST EIAV

描述：（改编自申请人的摘要） 可以帮助控制马传染性贫血病毒（EIAV）的反应似乎 重要是因为类似的机制可能适用于其他慢病毒 感染.假设免疫反应涉及 对EIAV的保护可以确定是基于对EIAV的最终控制， 马的疾病，并证明淋巴细胞反应是 负责控制。初始血浆病毒血症降低至 感染马中检测不到的水平与以下症状的出现有关： 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能检测到。的要求 Th1亚群的病原体特异性CD4+辅助性T淋巴细胞（HTL）活性， 通过细胞因子的产生来确定，有效的CTL应答是良好的。 记录在案。此外，对不同病毒系统的研究表明， 证明仅使用HTL表位的有效性，HTL表位引发强的CD4+ T细胞亚群。 Th1应答增强增殖和CTL活性， 病毒挑战慢病毒疫苗的这种方法可能会克服 难以鉴定通用CTL和HTL表位， 由广泛的主要组织相容性复合体I类或I类 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表位已定位于慢病毒的保守区域中 这可能会避免另一个关键的抗原变异问题。我们 长期的研究目标是确定HTL和CTL在控制中的作用， 为了实现这一目标，我们特别需要更多的 了解CD4+ T淋巴细胞对这种免疫力的贡献。与 最后，本提案中概述的实验将直接测试 假设诱导CD4+ Th1淋巴细胞对通用和 保守的EIAV表位将促进增强的CTL应答， 预防随后的EIAV攻毒。

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.