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 ofmemory 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 xperiments, 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.