NALT- versus PEYER'S-patch-mediated mucosal immunity

Key Points

• The common mucosal immune system consists of organized inductive sites and diffuse effector sites for the generation of antigen-specific mucosal immunity.

• In rodents, nasopharynx-associated lymphoid tissue (NALT) is found on both sides of the nasopharyngeal duct, dorsal to the cartilaginous soft palate, and it is considered to be analogous to Waldeyer's ring in humans.

• NALT is a site of IgA class-switch recombination, and T helper 1 (T _H1)- and T _H2-cell generation. In this way, it is an important inductive site for the generation of mucosal immunity in the aero-digestive tract, similar to Peyer's patches in the intestine.

• NALT-targeted immunization efficiently induces antigen-specific immune responses in both mucosal and systemic immune compartments, leading to a two-tiered immunological barrier.

• NALT tissue genesis begins after birth, whereas the organogenesis of Peyer's patches commences during the gestational period.

• A condition of 'programmed inflammation', such as that induced by the lymphotoxin-β receptor (LT-βR)–nuclear factor-κB-inducing kinase (NIK)-signalling cascade, is essential for the genesis of Peyer's patches, whereas NALT organogenesis is independent of this LT-βR–NIK-mediated inflammation.

• NALT organogenesis is also independent of the interleukin-7 receptor (IL-7R)-mediated tissue-genesis programme that is essential for the development of Peyer's patches.

• ID2 (inhibitor of DNA binding 2)-dependent, but not ROR-γ (retinoic-acid-receptor-related orphan receptor-γ)-dependent, CD3 ⁻CD4 ⁺CD45 ⁺ inducer cells are essential for NALT organogenesis.

• A thorough understanding of the unique molecular and cellular properties of NALT is important for the development of a successful intranasally administered vaccine.

Abstract

Recent studies indicate that the mechanism of nasopharynx-associated lymphoid tissue (NALT) organogenesis is different from that of other lymphoid tissues. NALT has an important role in the induction of mucosal immune responses, including the generation of T helper 1 and T helper 2 cells, and IgA-committed B cells. Moreover, intranasal immunization can lead to the induction of antigen-specific protective immunity in both the mucosal and systemic immune compartments. Therefore, a greater understanding of the differences between NALT and other organized lymphoid tissues, such as Peyer's patches, should facilitate the development of nasal vaccines.