CHARACTERIZATION OF SIV PROTECTIVE IMMUNITY IN MUCOSA: VAGINAL & CERVIX

入侵诱导的黏膜免疫应答的鉴定 粘膜的感染对于确定反应至关重要 对防止性传播至关重要。 为此我们 已经描述了固有层中存在的免疫反应 (LP)（11）恒河猴结肠暴露于SIV后 分子克隆 11只受感染的猴子中有4只带有很强的SIV 在LP中的env特异性、MHC I类限制性CTL应答。 三个或 暴露后6个月，这11只动物和4只未处理对照动物被 感染了致病性SIV 所有4只猴均具有强SIV LP中env特异性MHC I类限制性CTL受到保护; 而其余7只在LP或 未处理的对照被保护。 这些数据提供了第一个直接 粘膜感染可诱导SIV特异性免疫， 仍然局限于肠道相关组织。 有强烈 LP中SIV env特异性、MHC限制性C TL之间的相关性 和保护粘膜免受异源原发性 孤立。 我们在空肠LP中观察到了强的env特异性CTL 外周血DNA-PCR阴性的8只动物中有4只 在阴道中接种SIV/Delta B670 cl 12后， 致病嗜巨噬细胞病毒。 这些动物未进行循环 注射孕酮 阴道激发后 用SIV/Delta B670 rh（恒河猴生长病毒）在孕酮循环中 动物，仅一只动物（J 484）具有最强的env特异性 激发前CTL在激发后显示强env特异性CTL。 挑战. 只有J 484似乎只是短暂感染， 由零星阳性DNA-PCR指示。 所有其他动物 的PCR阳性结果显示， 各种组织，并进展到疾病状态。 资金 NIH/AI-35546 11/01/93-10/31/98 $243，147（最终年度）出版物 没有一

The identification of mucosal immune responses induced by invasion of the mucosae by HIV/SIV is essential to identifying responses critical to protection against sexual transmission. To this end, we have characterized the immune responses present in the lamina propria (LP) of (11) rhesus monkeys following colonic exposure to a SIV molecular clone. Four of the 11 infected monkeys had a strong SIV env-specific, MHC class I restricted CTL response in the LP. Three or 6 months post-exposure, these 11 animals and 4 naive controls were challenged with a pathogenic SIV. All 4 monkeys with strong SIV env-specific MHC Class I restricted CTL in the LP were protected; whereas, none of the remaining 7 monkeys without CTL in the LP or the naive controls were protected. These data provide the first direct evidence that mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. There was a strong correlation between SIV env-specific, MHC-restricted C TL in the LP and protection against mucosal challenge with a heterologous primary isolate. We have observed strong env-specific CTL in the jejunal LP of 4 of 8 animals that were DNA-PCR negative in peripheral blood following inoculation in the vagina with SIV/Delta B670 cl12, a pathogenic macrophage tropic virus. These animals were not cycled with progesterone prior to inoculation. Following vaginal challenge with SIV/Delta B670 rh (rhesus grown virus) in progesterone cycled animals, only one animal (J484) that had the strongest env-specific CTL before challenge displayed strong env-specific CTL after challenge. Only J484 appeared to be only transiently infected as indicated by the sporadically positive DNA-PCR. All other animals were persistently infected as shown by positive PCR results from various tissues and progressed into the disease state. FUNDING NIH/AI-35546 11/01/93-10/31/98 $ 243,147 (Final Year) PUBLICATIONS None