Identification of SIV env-specific CTL in the jejunal mucosa in vaginally exposed, seronegative rhesus macaques (Macaca mulatta)

We previously reported major histocompatibility complex Class I-restricted cytotoxic T lymphocytes (CTL) in jejunal lamina propria (LP) of monkeys fol lowing colonic exposure to subinfectious SIV doses. Those monkeys with stro ng mucosal CTL responses specific for simian immunodeficiency virus (SIV) e nvelope (env) were protected from later colonic challenge with a heterologo us pathogenic virus dose. Here, env-specific CTL were similarly induced in jejunal LP in five of eight non-progesterone treated macaques that were vag inally exposed to SIV, but not infected. Subsequent vaginal challenge follo wing progesterone treatment produced systemic infection. The only two monke ys that had jejunal env-specific CTL detectable post-challenge developed si gnificantly lower plasma virus loads, and had delayed disease progression. Either vaginal or colonic exposure to subinfectious SIV doses can induce CT L detectable in jejunal LP. The association of such CTL with protection or delayed disease upon challenge suggests that successful vaccine protection against SIV/HIV may require CTL responses in the mucosa.