Mucosal surfaces of the body serve as the major portal of entry for HIV. These tissues also house a majority of the body's lymphocytes, including the CD4+ T-cells that are the major cellular target for HIV infection. Elucidating mucosal immune responses is critical to our understanding of the host–pathogen relationship for two reasons: first, mucosal barriers are defended by a range of innate and adaptive defenses that might be exploited to develop effective vaccines or microbicides; second, adaptive immune responses in mucosal lymphoid tissues might serve to limit viral replication, decreasing the host's viral burden as well as reducing the likelihood of sexual transmission to a naïve host.