Immature, Semi-mature and Fully Mature Dendritic Cells: Which Signals Induce Tolerance or Immunity?

Dendritic cells (DCs) are currently divided into tolerogenic immature and immunogenic mature differentiation stages. However, recent findings challenge this model by reporting mature DCs as inducers of regulatory CD4+ T cells in vivo. This implies that decisive tolerogenic and immunogenic maturation signals for DCs might exist. Closer inspection reveals that tolerance is observed when partial- or semi-maturation of DCs occurs, whereas only full DC maturation is immunogenic. The decisive immunogenic signal seems to be the release of proinflammatory cytokines from the DCs. Moreover, the semi-mature DC phenotype is comparable to steady-state migratory veiled DCs within the lymphatics, which seem to continuously tolerize lymph node T cells against tissue-derived self-antigens or apoptotic cells.