PLOS Pathogens: Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response
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In a study comparing infant mice to older animals, NIAID scientists found a number of differences in the way mobile immune system cells called dendritic cells behave in response to respiratory syncytial virus (RSV). For example, in infant mice, one subset of dendritic cells has far fewer critical co-stimulatory molecules present on the cell surface as compared to those of older animals. The dearth of these co-stimulatory molecules means infant lungs mount a less effective response to RSV. The authors of the study, which appeared Feb. 13 in the open-access journal PLOS Pathogens, say knowledge about infant immune responses could be exploited to design pediatric RSV vaccines that elicit an adult-like immune response.
The paper, “Quantitative and qualitative deficits in neonatal lung-migratory dendritic cells impact the generation of the CD8+ T cell response” is available online /bit.ly/1jDy25L
Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response
- Published: February 13, 2014
- DOI: 10.1371/journal.ppat.1003934
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.
Author Summary
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. Disease is a consequence of virus- and T-cell-mediated pathology. Adaptive immune responses to viral respiratory infections are initiated by dendritic cells (DCs) that traffic to lymph nodes from the infected lungs. We compared the phenotype and function of two lung-migratory DC populations, identified by high expression of MHC Class II and CD103+ (CD103+DCs) or CD11b+ (CD11b+DCs), in mice infected in early life or as adults. We found that DC subsets undergo dramatic quantitative and qualitative changes during the first weeks of life, and CD103+DCs from neonatal mediastinal lymph nodes induced a fundamentally different CD8+ T-cell response profile than CD103+DCs from adults. The adult response pattern required CD28-mediated costimulatory signals, which is a limiting functional property of neonatal CD103+DCs. Thus, the ability of neonatal CD103+DCs to provide sufficient costimulation to neonatal CD8+ T-cells can influence the immunodominance hierarchy and functional properties of neonatal CD8+ T-cell responses compared to those of adults. A better understanding of deficiencies in early life immunity will guide vaccine approaches that induce disease-sparing immune responses in infants.
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