CHARACTERIZATION OF SIV PROTECTIVE IMMUNITY IN MUCOSA: VAGINAL & CERVIX

粘膜中 SIV 保护性免疫的特征：阴道

• 批准号: 6116190
• 负责人: LAWRENCE A. WILSON
• 金额: $ 5.31万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116190
• 关键词: AIDS; Mammalia; animal tissue; communicable diseases; immunology; inflammation; intestines; lymphatic system; vaccines; virus

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

入侵诱导的粘膜免疫反应的鉴定 HIV/SIV 对粘膜的影响对于确定反应至关重要 对于防止性传播至关重要。 为此，我们 表征了固有层中存在的免疫反应 (11) 恒河猴结肠暴露于 SIV 后的 (LP) 分子克隆。 11 只受感染的猴子中有 4 只具有强 SIV 环境特异性、MHC I 类限制 LP 中的 CTL 反应。 三或 暴露后 6 个月，这 11 只动物和 4 只未实验的对照组 受到致病性 SIV 的攻击。 所有 4 只猴子均具有强 SIV LP 中环境特异性 MHC I 类限制性 CTL 受到保护； 然而，剩下的 7 只猴子在 LP 或 幼稚的控制受到保护。 这些数据提供了第一个直接的 有证据表明粘膜感染可诱导 SIV 特异性免疫 仍然局限于肠道相关组织。 有一种强烈的 LP 中 SIV env 特异性、MHC 限制性 C TL 之间的相关性 和保护免受异源原发性粘膜挑战 隔离。 我们在空肠 LP 中观察到强环境特异性 CTL 8 只动物中有 4 只的外周血 DNA-PCR 呈阴性 在阴道内接种 SIV/Delta B670 cl12 后， 致病性巨噬细胞嗜性病毒。 这些动物没有骑自行车 接种前用黄体酮。 阴道挑战后 黄体酮循环中含有 SIV/Delta B670 rh（恒河猴生长病毒） 动物，只有一种动物（J484）具有最强的环境特异性 挑战前的 CTL 在挑战后表现出强烈的环境特异性 CTL 挑战。 只有 J484 似乎只是暂时感染，因为 偶发阳性 DNA-PCR 表明。 所有其他动物 PCR 阳性结果显示，持续感染 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（最后一年）出版物 没有任何