ID: 250. Issue 1 (November 2015) - Tomisawa, Mio Angelica
Abstract Surviving infection requires a careful balance of pro-inflammatory signals that promote pathogen clearance and anti-inflammatory signals that prevent immunopathology. The activation and expansion of regulatory T cells (Treg) is key to this balance. FoxP3+ Treg have been shown to acquire certain characteristics of effector T cells when activated in polarized immune responses, expressing Tbet during a Th1 infection and acquiring GATA3 expression during a Th2 response. It is controversial whether these new transcription factors are evidence of conversion to pro-inflammatory effector T cells, or are a mechanism by which the Treg become adapted to their environment and acquire enhanced suppressive function. We have observed that, during respiratory infection with Influenza A virus, approximately 30% of FoxP3+ Treg expressed the potent immunosuppressive cytokine, IL-10. All of the IL-10+ Tregs were also positive for Tbet. Our hypothesis is that the same cytokine signals needed for the induction of IL-10 are also responsible for the initiation of Tbet expression, suggesting that the adaption of Treg cells to their environment facilitates better immunosuppression. We will examine the effects of IL-12, IL-27 and other inflammatory signals on the Tbet expression, IL-10 production and suppressive function of FoxP3+ Tregs both in vitro and in vivo. Our data will elucidate the molecular signals required for optimal disease protection by FoxP3 Tregs in vivo.