Abstract
In this study, we have analyzed the in vivo dynamics of the interaction between polyclonal Foxp3^+^ Treg cells, effector T (Teff) cells, and DCs in order to further our understanding of the mechanisms of Treg cellโmediated suppression. Cotransfer of polyclonal activated Treg cells into healthy mice attenuated the induction of EAE. Suppression of disease strongly correlated with a reduced number of Teff cells in the spinal cord, but not with Treg cellโmediated inhibition of Th1/Th17 differentiation. Cotransfer of Treg cells with TCRโTg Teff cells followed by immunization by multiple routes resulted in an enhanced number of Teff cells in the lymph nodes draining the site of immunization without an inhibition of Teffโcell differentiation. Fewer Teff cells could be detected in the blood in the presence of Treg cells and fewer T cells could access a site of antigen exposure in a modified delayedโtype hypersensitivity assay. Teff cells recovered from LNs in the presence of Treg cells expressed decreased levels of CXCR4, syndecan, and the sphingosine phosphate receptor, S1P1 (sphingosine 1โphosphate receptor 1). Thus, polyclonal Treg cells influence Teffโcell responses by targeting trafficking pathways, thus allowing immunity to develop in lymphoid organs, but limiting the number of potentially autoโaggressive cells that are allowed to enter the tissues.