Respiratory Syncytial Virus Disease Severity is Associated with Distinct CD8+ T Cell Profiles.

Abstract

RATIONALE\nRespiratory syncytial virus (RSV) presents causes significant morbidity and mortality in infants worldwide. Although T helper type 2 (Th2) pathology is implicated in severe disease, the mechanisms underlying the development of immunopathology are incompletely understood.\n\n\nOBJECTIVES\nWe aimed to identify local immune responses associated with severe respiratory syncytial virus disease in infants. Our hypothesis was that disease severity would correlate with enhanced Th2 cellular responses.\n\n\nMETHODS\nNasal aspirates were collected from infants hospitalized with severe (admitted to the pediatric intensive care unit) or moderate (maintained in the general ward) RSV disease at 7 days after enrollment. The immune response was investigated by evaluating T lymphocyte cellularity, cytokine concentration, and viral load.\n\n\nMEASUREMENTS AND MAIN RESULTS\nSevere patients had increased proportions of CD8+ T cells expressing IL-4 (Tc2) and reduced proportions of CD8+ T cells expressing IFNγ (Tc1). Nasal aspirates from severe patients 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.\n\n\nCONCLUSIONS\nSevere RSV disease was associated with distinct T cell profiles. Tc1, Tc17, and Th17 may play protective roles in RSV infection, while Tc2 cells may play a previously underappreciated role in pathology.