Tolerogenic dendritic cells differentially modulate naïve and memory CD4⁺ T cells

Dendritic cells (DC) can be alternatively activated to induce tolerogenic DC, making them a promising therapy for autoimmunity. Because naïve and memory T cells have different requirements for tolerisation, we tested the modulatory activity of tolerogenic DC on both subsets of T cells.

Human monocyte-derived DC were matured with lipopolysaccharide (LPS-DC) or treated with dexamethasone, vitamin D3 and lipopolysaccharide (LPS-DexD3 DC) to obtain tolerogenic DC. DC were cocultured with allogeneic naïve or memory CD4⁺ T cells. Primed T cells were rested and restimulated with LPS-DC or CD3/CD28 beads.

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.