ADOPTIVE TRANSFER OF CD8+ CTLS TO CONTROL EIAV

研究建议：本研究的长期目标是确定 CTL在控制EIAV中的作用，EIAV是一种引起马的慢病毒， 以反复发作的病毒血症为特征的持续感染， 并发发热、血小板减少和贫血。感染EIAV的马 最终控制病毒血症和相关的临床疾病， 终身隐性携带者使用受严重影响的马驹工作 联合免疫缺陷（SCID）已经表明，淋巴细胞反应是 需要终止急性感染后的病毒血症。此外，本发明还提供了一种方法， 持续的免疫控制机制可能是导致 维持隐性携带状态，如复发所示 免疫抑制后的临床疾病。EIAV- 特异性CD 8 + CTL的检测与细胞周期的终止一致。 急性感染后，在出现病毒血症之前，出现初始病毒血症 中和抗体，表明CTL参与控制 病毒血症。此外，隐性携带者在PBMC中具有EIAV特异性CTLm。 拟议的研究将检验EIAV特异性CD 8 + CTL将预防或减少EIAV攻毒后的病毒血症。在 特异性目的，来自PBMC的Env和Gag/Pr特异性CD 8 + CTL， 将使用逆转录病毒筛选、刺激和扩增携带者。 载体转导的自体马肾刺激细胞，和 过继转移至ELA-A匹配的SCID马驹。这些小马驹将 感染EIAV并确定保护作用。如果小马驹 受保护，CD 8 + CTL的保护作用特异于 将评价保守的Gag蛋白p15、p26 a和p26 b。结果 这项研究应该提供深入了解免疫机制， 控制其他慢病毒感染，包括HIV-1。

Research Proposal: The long-term goal of this research is to define the role of CTLs in the control of EIAV, a lentivirus of horses which cause a persistent infection characterized by recurrent episodes of viremia with concurrent fever, thrombocytopenia, and anemia. Horses infected with EIAV eventually control the viremia and associated clinical disease, and remain lifelong inapparent carriers. Work using foals affected with severe combined immunodeficiency (SCID) has shown that lymphocyte responses are required to terminate the viremia following acute infection. In addition, continued immunologic control mechanisms are likely responsible for maintenance of the inapparent carrier state, as evidenced by recrudescence of clinical disease following immunosuppression. The fact that EIAV- specific CD8+ CTLs are detected con-incident with the termination of the initial viremia following acute infection, prior to the appearance of neutralizing antibody, suggests that CTLs are involved in control of viremia. In addition, inapparent carriers have EIAV-specific CTLm in PBMC. The proposed research will test the hypothesis that EIAV-specific CD8+ CTLs will prevent or reduce viremia following EIAV challenge. In the specific aims, Env and Gag/Pr-specific CD8+ CTLs from PBMC from inapparent carriers will be selected, stimulated and expanded using retroviral vector-transduced autologous equine kidney stimulator cells, and adoptively transferred to ELA-A matched SCID foals. These foals will then be infected with EIAV and the protective effects determined. If the foals are protected, the protective effects of CD8+ CTLs specific for the conserved Gag proteins p15, p26a, and p26b will be evaluated. The results of this research should provide insight into the mechanisms of immune control of other lentiviral infections, including HIV-1.