Abstract
CD103+ and CD11b+ populations of CD11c+MHCIIhi murine dendritic cells (DCs) have been shown to carry antigens from the lung through the afferent lymphatics to mediastinal lymph nodes (MLN). We compared the responses of these two DC populations in neonatal and adult mice following intranasal infection with respiratory syncytial virus. The response in neonates was dominated by functionally-limited CD103+ DCs, while CD11b+ DCs were diminished in both number and function compared to adults. Infecting mice at intervals through the first three weeks of life revealed an evolution in DC phenotype and function during early life. Using TCR transgenic T cells with two different specificities to measure the ability of CD103+ DC to induce epitope-specific CD8+ T cell responses, we found that neonatal CD103+ DCs stimulate proliferation in a pattern distinct from adult CD103+ DCs. Blocking CD28-mediated costimulatory signals during adult infection demonstrated that signals from this costimulatory pathway influence the hierarchy of the CD8+ T cell response to RSV, suggesting that limited costimulation provided by neonatal CD103+ DCs is one mechanism whereby neonates generate a distinct CD8+ T cell response from that of adults.
Highlights
Four major populations of dendritic cells have been defined in lung [1,2,3]
Respiratory syncytial virus (RSV) infection is most severe in infants under six months and the most common cause of hospitalization for lower respiratory tract infection in children under five years
Adaptive immune responses to viral respiratory infections are initiated by dendritic cells (DCs) that traffic to lymph nodes from the infected lungs
Summary
Four major populations of dendritic cells have been defined in lung [1,2,3]. Plasmacytoid DCs (pDCs) and two migratory dendritic cell populations, distinguished by the expression of either CD103 or CD11b, are responsible for lung surveillance in the steady-state and are poised to detect and respond rapidly to environmental and microbial threats. Recent studies have revealed specialization of these subsets, and a critical role for the CD103+ and CD11b+ tissue-resident populations of DCs in the induction of the adaptive response. CD103+ DCs, primarily located in the basal lamina, and CD11b+ DCs, situated in the lamina propria, are the two populations capable of capturing antigen and migrating through afferent lymphatics to mediastinal lymph nodes (MLN) to initiate and orchestrate adaptive immune responses. CD103+ DCs, and the related CD8a+ lymph node-resident DC subset, readily crosspresent antigens [4,5], and CD103+ DCs have been shown to potently induce CD8+ T cell responses [6,7,8,9,10,11]. The composition and function of these two types of dendritic cell in the MLN is likely to dictate the outcome of adaptive immune responses
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