LPS-DexD3 DC have reduced stimulatory capacity for both naïve and memory T cells. However, restimulation of T cells revealed a distinct difference between naïve and memory T cells that had been primed by LPS-DexD3 DC. Naïve T cells did not become anergic but were skewed to a regulatory phenotype (low IFNγ and high IL-10 production), whereas memory T cells were rendered hyporesponsive, with low proliferation and cytokine production. Thus, naïve and memory T cells are differently regulated by LPS-DexD3 DC. These data have implications for the use of tolerogenic DC vaccines as immunomodulators.