MUCOSAL IMMUNITY TO SIV INFECTION & VACCINES

侵袭诱导的粘膜免疫反应的鉴定 HIV/SIV对粘膜的检测对于识别应答是必不可少的 对防止性传播至关重要。最好的目标 因为这些研究是那些在粘膜上 暴露在病毒中，但不会持续感染。对这件事 最后，我们已经确定了椎板中存在的免疫反应 空肠、肠系膜淋巴结的固有层(LP)和上皮 11只恒河猴结肠暴露后的外周血 至(2)SIV分子克隆(4个SIVmac 239和7个SIV/17E-Fr)。其中四个 被感染的猴子有很强的SIV环境特异性，MHC I类 限制了LP的CTL反应；而只有一只动物有SIV 脂蛋白中产生环境特异性IgA的B细胞。三到六个月 暴露后，这11只动物和4只幼稚的对照组受到了挑战 用高剂量的异源初级分离物进行结肠内注射， SIV/DeltaB670。所有四只猴子都具有强烈的SIV环境特异性MHC LP中的I类受限CTL受到保护；而 其余7只在LP和幼稚对照组中没有CTL的猴子是 受到保护。这些数据提供了第一个直接的证据 感染可诱导SIV特异性免疫，这种免疫仍局限于 与肠道相关的组织。此外，还有一个很强的 扁平苔藓中SIV env特异性MHC限制性CTL与 异源原代细胞对黏膜攻击的保护 隔离。我们还开始了使用6 SIV/17E-Fr的纵向研究 6只SIV/DeltaB670动物直肠接种，而不是 从殖民地上讲。分别于术后1、2、3、4、8周进行检测 接种外周血中的CTL。手术是在 分别于1、3、8周测定空肠液化液中的CTL。看起来好像 强烈的环境特异性CTL反应发生在不同的时间点 在6只接种SIV/17E-Fr的动物中有4只在PBMC和LP中检测到SIV/17E-Fr。 CTL的诱导在高致病性患者中不明显 SIV/DeltaB670接种动物。这些动物

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. The best target for these studies are those individuals who have been mucosally exposed to virus but do not become persistently infected. To this end, we have characterized the immune responses present in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes and peripheral blood of 11 rhesus monkeys following colonic exposure to (2) SIV molecular clones (4 SIVmac 239 and 7 SIV/17E-Fr ). Four of the infected monkeys had a strong SIV env-specific, MHC class I restricted CTL response in the LP; whereas only one animal had SIV env-specific IgA-producing B cells in the LP. Three or 6 months post-exposure, these 11 animals and 4 naive controls were challenged intracolonically with a high dose of the heterologous primary isolate, SIV/DeltaB670. All four 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. Furthermore, there was a strong correlation between SIV env-specific, MHC-restricted CTL in the LP and protection against mucosal challenge with a heterologous primary isolate. We also have begun a longitudinal study using 6 SIV/17E-Fr and 6 SIV/DeltaB670 animals inoculated rectally rather than colonically. Assays were conducted at 1, 2, 3, 4 and 8 wks post inoculation for CTL in peripheral blood. Surgeries were performed at 1, 3, and 8 wks to assay for CTL in the jejunal LP. It would seem that strong env-specific CTL responses occur at different time points in the PBMC and LP among 4 of the 6 SIV/17E-Fr inoculated animals. The induction of CTL is less obvious in the highly pathogenic SIV/DeltaB670 inoculated animals. These animals