Defective regional immunity in the respiratory tract of neonates is attributable to hyporesponsiveness of local dendritic cells to activation signals.
A variety of studies suggest that the increased susceptibility of neonates to allergic and infectious respiratory diseases is due to delayed postnatal maturation of local mucosal immune function. We have recently demonstrated that the postnatal development of the major resident APC population in the respiratory tract (RT), class II MHC (Ia)-bearing dendritic cells (DC), is delayed relative to that in other tissues, and that both the intensity of Ia expression on these RTDC and their density within respiratory epithelia remain low until after weaning. The present study focuses on the functional capacity of neonatal RTDC and their responses to exogenous stimuli, and demonstrates that 1) infant Ia+ RTDC respond poorly to GM-CSF, under conditions that stimulate high levels of Ia expression and concomitant APC activity in adult cells; 2) both infant and adult RTDC contain a subpopulation of Ia- cells recognized by mAb OX62 that also respond poorly to GM-CSF; 3) inhalation of microbial stimuli or parenteral administration of IFN-gamma triggers rapid recruitment of DC into the airway epithelium and lung parenchyma of adults; this response is markedly attenuated in newborns and does not attain levels of competence until after weaning; and 4) endogenous macrophage-mediated suppression of the RTDC response to GM-CSF, the principal mechanism limiting in situ DC functional maturation in the adult lung, is highly active in the neonates. Taken together with earlier evidence of the relatively rapid postnatal development of T and B cell function in these animals, the present findings suggest that the sluggish performance of respiratory mucosal immune function(s) during infancy is attributable primarily to delayed maturation of local DC populations.
Nelson
D J
DJ
TVW Telethon Institute for Child Health Research, West Perth, Western Australia, Australia.
Holt
P G
PG
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D017951:Antigen Presentation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology*; D051381:Rats; D012137:Respiratory System / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor