IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction — A comparative study of human clinical-applicable DC

Tolerogenic dendritic cells (tDC) are a promising tool for specific cellular therapy to induce immunological tolerance in transplantation and autoimmunity. To date, most described tDC methods have not been converted into clinically applicable protocols and systematic comparison of required functional characteristics, i.e. migration and functional regulatory T cell (Treg) induction, is lacking. We compare clinical-grade tDC generated with vitamin D3, IL-10, dexamethasone, TGFβ or rapamycin. For good migratory capacity and a stable phenotype, additional maturation of tDC was required. Maturation with a cocktail of TNFα, IL-1β and PGE2 induced optimal migration. Importantly, all tDC showed a stable phenotype under pro-inflammatory conditions. Especially IL-10 DC showed most powerful tolerogenic characteristics with high IL-10 production and low T cell activation. Moreover, in a functional suppression assay only IL-10 DC induced Treg that strongly suppressed T cell reactivity. Thus, clinical-grade IL-10 DC show functional characteristics that make them best suited for tolerance-inducing therapies.

► Generation of clinical-grade tolerogenic DC with VD3, IL-10, dex, TGFβ or rapa.
► Functional comparison of clinical-grade tolerogenic DC.
► Co-maturation of tolerogenic DC is required for migration and stability.
► Suppression assay shows that IL-10 DC induce best functional Treg.
► In GMP protocol IL-10 DC are most powerful tolerogenic DC for clinical application.