TARGETED DELIVERY OF ANTIGEN TO HAMSTER NASAL LYMPHOID-TISSUE WITH M-CELL-DIRECTED LECTINS

The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological funct ions, Aggregates of nasal lymphoid tissue (NALT) located at the base o f the nasal cavity are believed to be sites of induction of mucosal im mune responses to airborne antigens, The epithelium overlying NALT con tains M cells which are specialized for the transcytosis of immunogens , as demonstrated in other mucosal tissues, We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which i nfluence antigen uptake and immune responses to transcytosed antigens, To identify glycoconjugates that may distinguish NALT M cells from ot her cells of the respiratory epithelium (RE), we performed lectin hist ochemistry on sections of the hamster nasal cavity with a panel of lec tins, Many classes of glycoconjugates were found on epithelial cells i n this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing cw-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively, By morphological criteria, the FAE contains >90% M cells, To determine i f apical glycoconjugates on M cells were accessible from the nasal cav ity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did no t, Lectin bound to M cells in vivo was efficiently endocytosed, consis tent with the role of hi cells in antigen transport, Intranasal immuni zation with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone o r admixed with lectin did not. The selective recognition of NALT M cel ls by a lectin in vivo provides a model for microbial adhesin-host cel l receptor interactions on M cells and the targeted delivery of immuno gens to NALT following intranasal administration.