Induction of regulatory T cells by a novel immunoregulatory therapy suppresses the development of allergic airways disease (97.10)

Abstract

Abstract Evidence suggests that exposure to Streptococcus pneumoniae may be protective against asthma. We have identified key S. pneumoniae components that form an immunoregulatory therapy (IRT) and suppress the development of allergic airways disease (AAD) using mouse models. AAD was induced in adult BALB/c mice by intraperitoneal sensitization and intranasal challenge with ovalbumin. At the time of sensitization, the IRT was administered intratracheally. IRT treatment suppressed hallmark features of AAD including eosinophil influx, local and systemic Th2 cytokines, airways hyperresponsiveness and mucus hypersecretion. A time course analysis showed that the IRT induced CD4+CD25+Foxp3+ Tregs in the lymph nodes 4 days post treatment. This was associated with increased IL-2, TGF-β and Foxp3 expression in the lungs. IRT treatment also increased the proportion of CD4+CD25+/- cells expressing Foxp3 in the lungs and expression of markers associated with Treg function, during the induction of AAD. Anti-CD25 administration 3 days before IRT treatment abolished the suppressive effects on AAD. However, anti-CD25 administration 9 days after IRT treatment had no effect. This indicated a requirement for IL-2 signalling via CD25 (IL-2R) during the induction of Tregs by the IRT treatment. In conclusion, a S. pneumoniae-based IRT induces CD25-dependent Tregs, suppresses the development of AAD and may be useful as a novel therapy for asthma.