DEVELOPMENT OF THE AIRWAY INTRAEPITHELIAL DENDRITIC CELL NETWORK IN THE RAT FROM CLASS-II MAJOR HISTOCOMPATIBILITY (IA)-NEGATIVE PRECURSORS- DIFFERENTIAL REGULATION OF IA EXPRESSION AT DIFFERENT LEVELS OF THERESPIRATORY-TRACT

The relative inefficiency of respiratory mucosal immune function durin g infancy is generally attributed to the immaturity of the neonatal T cell system. However, immune competence in the adult lung has recently been shown to be closely linked to the functional capacity of local n etworks of intraepithelial dendritic cells (DC). This study examines t he density and distribution of these DC throughout the neonatal respir atory tract in rats, focusing particularly on microenvironmental regul ation of their class II major histocompatibility complex (MHC) (Ia) ex pression. In animals housed under dust-controlled conditions, airway e pithelial and alveolar Ia(+) DC detectable by immunostaining with the monoclonal antibody (mAb) Ox6 are usually not seen until day 2-3 after birth, and adult-equivalent staining patterns are not observed until after weaning. In contrast, the mAb Ox62 detects large numbers of DC i n fetal, infant, and adult rat airway epithelium. Costaining of these Ox62(+) DC with Ox6 is rare in the neonate and increases progressively throughout infancy, and by weaning Ia(+) DC comprised, on average, 65 % of the overall intraepithelial DC population. In infant rats, Ia(+) DC are observed first at the base of the nasal turbinates, sites of ma ximum exposure to inhaled particulates, suggesting that their maturati on is driven in part by inflammatory stimuli. Consistent with this sug gestion, densitometric analysis of Ia staining intensity of individual DC demonstrates that by 2-3 d after birth, Ia expression by nasal epi thelial DC was comparable with that of Ia(high) epidermal Langerhans c ells in adjacent facial skin, at a time when expression by tracheal ep ithelia DC was 7-10-fold lower. Additionally, the rate of postnatal ap pearance of Ia(high) DC in the airway epithelium was increased by admi nistration of interferon gamma, and decreased by exposure of infant ra ts to aerosolized steroid. These findings collectively suggest that Ia expression by neonatal respiratory tract DC is locally controlled and can be upregulated by mediators that are produced within the lung and airway epithelium in response to inhalation of proinflammatory stimul i. It was also noted that Ia(low) neonatal airway DC expressed adult e quivalent levels of class I MHC, which suggests differences in capacit y to prime for CD8(+)-dependent versus CD4(+)-dependent immunity to in haled pathogens, during the early postnatal period.