Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 201, Issue 3, Pages 325-334Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.201903-0588OC
Keywords
RSV; infant; adaptive; immunity
Categories
Funding
- National Institutes of Health (National Institute of Allergy and Infectious Diseases) [AI090059]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES015050] Funding Source: NIH RePORTER
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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 IFN-gamma (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.
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