A revisit of mucosal IgA immunity and oral tolerance

Induction of mucosal immunity by oral immunization with protein antigen alo ne is difficult: potent mucosal adjuvants vectors, or other special deliver y systems are required. Cholera toxin (CT) has been shown to be an effectiv e adjuvant for the development of mucosal vaccines and, when given with vac cine, induces both mucosal and systemic immune responses via a Th2 cell-dep endent pathway. However, and in addition to potential type-I hypersensitivi ty, a major concern for use of mucosal adjuvants such as CT is that this mo lecule is not suitable for use in humans because of its inherent toxicity. When we examined the potential toxicity of CT for the central nervous syste m, both CT and CT-B accumulated in the olfactory nerves/epithelium and olfa ctory bulbs of mice when given by the nasal route. The development of effec tive mucosal vaccines for the elderly is also an important issue; however, only limited information is available. When mucosal adjuvanticity of CT was evaluated in aged mice, an early immune dysregulation was evident in the m ucosal immune system. The present review discusses these potential problems for effective mucosal vaccine development. Tolerance represents the most c ommon and important response of the host to environmental antigens, includi ng food and commensal bacterial components, for the maintenance of an appro priate immunological homeostasis. We have examined whether Peyer patches co uld play a more important role for the maintenance of oral tolerance. Using Peyer patch-null mice, we found that mice lacking this gut-associated lymp hoid tissue retained their capability to produce secretory IgA antibodies b ut did not develop normal oral tolerance to protein antigens.