CHARACTERIZATION OF SIV PROTECTIVE IMMUNITY IN MUCOSA: VAGINAL & CERVIX

点击翻译按钮获取中文摘要

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