Most studies of antiviral immunity have focused on peripheral blood. However, the majority of lymphocytes are harbored in lymphoid tissues throughout the body. Mucosal lymphoid tissues serve as a portal of entry for HIV and as a site of active viral replication and CD4+ T-cell depletion. Therefore, studies of mucosal immunity are of particular importance for our understanding of HIV pathogenesis. Understanding the induction of antiviral immunity at mucosal surfaces is also of great relevance for vaccine development, as the majority of HIV transmission occurs through sexual contact.