Respiratory syncytial virus disease severity is associated with distinct CD8+ T-cell profiles
Copyright © 2020 by the American Thoracic Society. Rationale: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Although T-helper type 2 (Th2) cell pathology is implicated in severe disease, the mechanisms underlying the development of immunopathology are incompletely understood. Objectives: We aimed to identify local immune responses associated with severe RSV in infants. Our hypothesis was that disease severity would correlate with enhanced Th2 cellular responses. Methods: Nasal aspirates were collected from infants hospitalized with severe (admitted to the pediatric ICU) or moderate (maintained in the general ward) RSV disease at 5 to 9 days after enrollment. The immune response was investigated by evaluating T-lymphocyte cellularity, cytokine concentration, and viral load. Measurements and Main Results: Patients with severe disease had increased proportions of CD8 (cluster of differentiation 8)- positive T cells expressing IL-4 (Tc2) and reduced proportions of CD8+ T cells expressing IFNγ (Tc1). Nasal aspirates from patients with severe disease had reduced concentrations of IL-17. Patients with greater frequencies of Tc1, CD8+ T cells expressing IL-17 (Tc17), and CD4+ T cells expressing IL-17 (Th17) had shorter durations of hospitalization. Conclusions: Severe RSV disease was associated with distinct T-cell profiles. Tc1, Tc17, and Th17 were associated with shorter hospital stay and may play a protective role, whereas Tc2 cells may play a previously underappreciated role in pathology.
Publication Source (Journal or Book title)
American Journal of Respiratory and Critical Care Medicine
Siefker, D., Vu, L., You, D., McBride, A., Taylor, R., Jones, T., DeVincenzo, J., & Cormier, S. (2020). Respiratory syncytial virus disease severity is associated with distinct CD8+ T-cell profiles. American Journal of Respiratory and Critical Care Medicine, 201 (3), 325-334. https://doi.org/10.1164/rccm.201903-0588OC