CD103int CCR7+ cDCs in Neonatal Lungs have Poor Antigen Presenting Capacity that Limits T Cell Responses Under Non-Inflammatory Conditions

The neonatal immune system must rapidly distinguish newly encountered environmental antigens and commensal organisms from pathogens without compromising the function of still-developing organs, such as the lung. Here we compared neontal (2-7 days) and adult (>6 weeks) conventional dendritic cells (cDCs) in the lung. We found that neonates had a greater frequency of pulmonary CD103⁺ cDCs than adults. The CD103⁺ cDCs in neonates were comprised of two populations, a CCR7⁺CD103^int population that was not observed in adults and a CCR7-CD103hi population that was similar to the population in adults. Alterations in the composition of pulmonary DCs in the neonate were not due to microbial exposure, as a similar composition was observed in neonatal and adult germ-free mice. The composition of DCs in the mediastinal lymph node (LN) reflected that in the lung, with a higher frequency CD103⁺ migratory DCs in neonatal LNs than in adult LNs. In neonates, the uptake, processing, and presentation of antigen was performed mostly by CD103^hi, followed by CD11b, and lastly CD103^int DCs. As a result, the T cell-priming capacity of neonatal DCs was limited and activated T cells produced more TNF-a than IL-4 or IFN-g. In summary, lung CD103^int CCR7⁺ cDCs are characteristic of the neonatal period and their low APC-activity contributes to poor T cell responses in the neonate.