Exploration of mucosal immunity in humans: relevance to vaccine development

Although the immune system is remarkably diverse, there is evidence that certain types of immune responses take place and are restricted to certain anatomic locations within the body. The concept of a common mucosal immune system that provides immune reactivity not only at the site of antigen deposition but also at remote mucosal sites may be explained by the utilization of organ-specific recognition molecules by circulating precursors of mucosal immunoblasts and by the production of certain maturation factors (e.g. cytokines, hormones) produced preferentially in certain organs or parts of a given organ. This notion may explain the unification of immune responses in diverse mucosal sites and the physiologic segregation of mucosal from systemic immune mechanisms. Novel methods have been developed to enable studies of antigen specific B and T cell responses in various mucosal and extramucosal tissues in primates and rodents, using cholera toxin or its B subunit as prototype immunogens and mucosal carrier-delivery systems. The tissue localization and isotype commitment of antibody-secreting cells (ASC) and the homing potential of their circulating precursors have also been examined after oral, nasal, intra-tonsillar, rectal and/or genital immunization(s). The anatomical distribution of T- and accessory cell-derived cytokines has also been examined. These tools and approaches are being employed in studies attempting to induce optimal mucosal immune responses to several mucosal pathogens including HIV-1, in certain organs such as the lower gastrointestinal tract and the female urogenital tract.(ABSTRACT TRUNCATED AT 250 WORDS)