Retinoic acid as an adjuvant to imprint mucosal homing properties to vaccine-induced T cells (39.32)

Abstract

Abstract Objective: All-trans retinoic acid (ATRA) induces the expression of gut-homing receptors on T cells during activation in vitro. We investigated the effect of ATRA as an in vivo adjuvant during vaccination on the formation and migration of memory T cells. Methods: T cells were analyzed in control and ATRA treated mice immunized with recombinant adenovirus expressing the LCMVgp33 epitope as well as following heterologous virus challenge. To directly compare the proliferative capacity and homing of memory cells from ATRA or vehicle-treated mice, these cells were co-transferred into recipients and responses analyzed following MVAgp33 challenge. Results: ATRA treatment during priming resulted in increased memory T cells in mucosal tissues and somewhat decreased splenic memory CD8 T cells. T cells primed in the context of ATRA exposure mounted stronger responses to systemic challenge with MVAgp33, and were more resistant to challenge with VVgp33 at vaginal surfaces. In co-transfer experiments, memory CD8 T cells from ATRA treated mice exhibited greater proliferation and increased gut homing. Conclusion: ATRA exposure during priming promotes the generation of memory T cells with greater proliferative potential and enhances mucosal localization. Thus ATRA may be a useful as an adjuvant during vaccination to enhance T cell responses at mucosal sites. This work is supported by the Bill & Melinda Gates Foundation.