Nasal-associated lymphoid tissue: Phenotypic and functional evidence for the primary role of peripheral node addressin in naive lymphocyte adhesion to high endothelial venules in a mucosal site

Nasal-associated lymphoid tissue (NALT), a mucosal inductive site for the u pper respiratory tract, is important for the development of mucosal immunit y locally and distally to intranasally introduced Ag, To more fully underst and the induction of nasal mucosal immunity, we investigated the addressins that allow for lymphocyte trafficking to this tissue. To investigate the a ddressins responsible for naive lymphocyte binding, immunofluorescent and i mmunoperoxidase staining of frozen NALT sections were performed using anti- mucosal addressin cell adhesion molecule-1 (MAdCAM-1), anti-peripheral node addressin (PNAd), and anti-VCAM-1 mAbs, All NALT high endothelial venules (HEV) expressed PNAd, either associated with MAdCAM-1 or alone, whereas NAL T follicular dendritic cells expressed both MAdCAM-1 and VCAM-1, These expr ession profiles were distinct from those of the gut mucosal inductive site, Peyer's patches (PP), The functionality of NALT HEV was determined using a Stamper-Woodruff ex vivo assay, The anti-L-selectin MEL-14 mAb blocked >90 % of naive lymphocyte binding to NALT HEV, whereas the anti-MAdCAM-1 mAb, w hich blocks almost all naive lymphocyte binding to PP, minimally blocked bi nding to NALT HEV, NALT lymphocytes exhibited a unique L-selectin expressio n profile, differing from both PP and peripheral lymph nodes. Finally, NALT HEV were found in increased amounts in the B cell zones, unlike PP REV, Th ese results suggest that NALT is distinct from the intestinal PP, that init ial naive lymphocyte binding to NALT HEV involves predominantly L-selectin and PNAd rather than alpha(4)beta(7)-MAdCAM-1 interactions, and that MAdCAM -1 and VCAM-1 expressed by NALT follicular dendritic cells may play an impo rtant role in lymphocyte recruitment and retention.