T cells in Group A Streptococcus infection: protection or pathology?

Streptococcus pyogenes (Group A Streptococcus; GAS) is a World Health Organization (WHO) priority pathogen for vaccine development. GAS vaccine development and trials have been impeded by a poor understanding of GAS immunity, and to date no correlate of protection has been identified. The predominant focus of efforts has been to establish antibody correlates of protection. However, T cell immunity may provide important contributions to clinical protection from GAS. This is supported by a possible relationship between the life-course ontogeny of T cell reactivity and repertoire compared with age-related GAS epidemiology. T cells are also the target of superantigens, a key GAS virulence mechanism. Furthermore, T cells have important functions in protection against other extracellular respiratory bacteria. Here, we explore immune risk factors associated with GAS epidemiology and clinical manifestations highlighting the dual protective (e.g. GAS-specific Th17 cells) and pathogenic (e.g. CD8+ T cells) role of T cells in GAS infection and how this could be harnessed in future research.