Respiratory syncytial virus disease severity is associated with distinct CD8+ T cell profiles

Abstract Most infants are infected with RSV by their second birthday. Despite known risk factors such as prematurity or congenital heart disease, most hospitalized infants are previously healthy. The mechanisms underlying the immunopathology of severe disease is incompletely understood. Our objective was to compare T cell profiles in nasal aspirates between infants with moderate and severe RSV disease hospitalized without immune deficiencies or congenital heart disease, during 2014–2017. Infants requiring intensive care were categorized as having severe disease, while infants maintained in the general ward were categorized as having moderate disease. The T cell profile in nasal aspirates collected 7 days after hospitalization (median 11 days after first symptom onset) was determined by flow cytometry. Nasal aspirates from patients with severe disease were characterized by a higher proportion of CD8+ T cells expressing IL-4 (Tc2) (P=0.024) and a lower proportion of CD8+ T cells expressing IFNγ (Tc1) (P=0.019) compared to patients with moderate disease. Patients with reduced frequencies of Tc1, Tc17, or Th17 cells had shorter durations of hospitalization (P=0.0023, P=0.0188, P=0.0437, respectively). Additionally, patients with severe disease had lower concentrations of IL-17 in nasal aspirates compared to patients with moderate disease (P=0.0133). These results suggest that RSV disease severity is associated with a specific T cell profile, and that Tc2 cells may play an underappreciated role in the development of RSV immunopathology.