Protective and dysregulated T cell immunity in RSV infection

Abstract

Respiratory syncytial virus (RSV) is the most important cause of infantile bronchiolitis and a major pathogen in elderly and immunosuppressed persons. Although RSV shows limited antigenic diversity, repeated infections occur throughout life. Vaccine development has been delayed by poor immunogenicity, production issues and the fear of causing enhanced disease. T cells assist in viral clearance, but immune regulation serves to limit these responses and to prevent the exaggerated inflammatory response to RSV infection seen in children with bronchiolitis. Severe RSV disease can therefore be regarded as a dysregulated response to an otherwise trivial infection. Further insights into the role of T cells (including Th17) are needed to enable the rational design of safe, effective vaccines and novel treatments.

Figure 1

The role of T cells in RSV clearance, protective immunity and immunopathology. RSV infects respiratory epithelial cells but impairs innate immune responses by inhibiting type I interferons and upregulating inhibitory molecules in the lung. Direct infection of dendritic cells also causes dysregulation of antigen presentation, leading to impaired T cell function, reduced viral clearance and memory formation. The T cell response is also skewed towards T cell subsets that enhance immunopathology but which may be limited by regulatory T cells. Proposed mechanisms by which RSV deranges the T cell response are shown in red text.