Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8⁺ T-Cell Profiles

Abstract

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 1 T cells expressing IFNg (Tc1). Nasal aspirates from patients with severe disease had reduced concentrations of IL-17. Patients with greater frequencies of Tc1, CD8 1 T cells expressing IL-17 (Tc17), and CD4 1 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.

Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

“…This is a result of impaired production of type-1-polarizing cytokines by neonatal DCs in response to stimulation through Toll-like Receptors (29, 105). This also affects the CD8 compartment, resulting in CD8 + T cells with a more type-2 phenotype (Tc2), which can exacerbate allergy-type reactions in asthma or infection with respiratory syncytial virus (RSV) (106)(107)(108)(109).Thus, the immune response generated by neonatal T cells is more of an innate nature, whereas adults produce cytokines that are typically associated with adaptive immune responses. Furthermore, neonatal T cells are less likely to secrete multiple cytokines simultaneously (110).…”

The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis

“…Peripheral blood gd T-cells of infants with severe disease failed to produce IFN-g when restimulated (14), whereas gd T-cells from neonatal mice had an impaired ability to produce IL-17 (15). Finally, Tc17 and Th17 cells were recently associated with shorter hospital stays and proposed to play a protective role (26). Altogether, our data demonstrate that the protective role of gd T-cells in RSV infection is largely inefficient in early life.…”

“…Remarkably, this transient type 2 cytokine environment was exacerbated upon RSV infection. So far, similar observations were only made at the systemic level or in nasal aspirates, and authors could only speculate on the relocation to the lower respiratory tract (26,50).…”

“…Recently, a study performed in hospitalized infants showed a possible involvement of Tc2 cells in disease severity. Although convincing, this study was for obvious ethical reasons restricted to nasal aspirates (26). Interestingly, Tc2 cells are increasingly proposed to play an important role in the etiology of asthma (48).…”

Multifunctional T cell response in convalescent patients two years after ZIKV infection

“…Whereas some reports associate Tc17 cells with virus resistance immunity in experimental models 26,67 and with children with respiratory syncytial virus infection, 72 some reports also associate Tc17 cells with increased pathology, especially when IFN is coproduced, in HBV infection, 73 tuberculosis, 23 experimental autoimmune encephalomyelitis, 74 autoimmune diabetes, 75 and psoriasis. 76 On the other hand, CD8+ T cells that produce IL-10 are associated with mild presentations of experimental coronavirus encephalitis 77 and dengue.…”