Induction of Th17 responses during vaccination: influence of route of immunization. (90.16)

Abstract

Abstract The role of Th17 cells in vaccine-induced immune responses is poorly understood. A growing body of evidence suggests that some adjuvants, such as cholera toxin from Vibrio cholerae and heat-labile toxin (LT) from Escherichia coli, can promote development of Th17 responses. We investigated the presence of Th17 cells after immunization with tetanus toxoid (TT) with and without the inclusion of a detoxified form of LT designated LT(R192G/L211A), or dmLT. Groups of BALB/c mice were immunized twice (day 0, 30) with TT alone or in conjunction with dmLT either mucosally (oral, intranasal, intrarectal) or parentally (subcutaneous). Animals were sacrificed 30 days after the last immunization and splenocytes were harvested for in vitro restimulation assays. Recipients of TT + dmLT by all mucosal routes had elevated levels of TT-specific Th17 cells compared to groups immunized parenterally or with TT alone by any route. Intranasal immunization with TT + dmLT induced particularly strong Th17 responses, with significant levels of IL-17 detected in antigen-restimulated splenocyte supernatants. Collectively, these results suggest that mucosal immunization in the presence of an appropriate immunostimulant, such as the adjuvant dmLT, can direct the development of Th17 responses. The observation that antien-specific Th17 cells were only detected following mucosal immunization suggests that Th17 responses may play a critical role in mucosal immune responses and mucosal vaccine-based protection.