Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa

The identification of mucosal immune responses required for protection agai nst sexual transmission of HIV is essential for the development of an effic acious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epitheliu m of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) o f 11 rhesus monkeys following colonic exposure to two molecular clones of S IV, Two monkeys had no signs of infection, Three monkeys became persistentl y infected. Transient infections, characterized by the sporadic detection o f virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the mo nkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP, Another transiently infected monkey had SIV-specific IgA secreting B ce lls in the LP, Three or six months postexposure, these animals and four nai ve controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670, All four monkeys with strong SIV env-specific MHC-r estricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protect ed. These experiments provide the first direct evidence that transient muco sal infection can induce SIV-specific immunity that remains localized to th e gut-associated tissues. Furthermore, a strong correlation between SIV env -specific MHC-restricted CTL in the LP and protection against colonic mucos al challenge was observed.