Figure 4.

Tolerogenic or immunogenic function of ICOS/ICOSL interaction depends on CD28 signaling. Immature DC express low amounts of CD28 ligands and thereby provide strong ICOS signals. This leads to stabilization of IL-10R on the surface of stimulated naïve T cells. Subsequently, the immunomodulatory cytokine IL-10 produced by DC mediates its function resulting in the differentiation into anergic Treg. In contrast, mature DC provide strong CD28 signals that overcome the tolerogenic ICOS function resulting in stabilization of IL-2 mRNA and synthesis and thereafter, the differentiation into inflammatory T effector cells.