Prolonged exposure of dendritic cells to maturation stimuli favors the induction of type‐2 cytotoxic T lymphocytes

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Abstract
Dendritic cell (DC) maturation influences the priming and polarization of T lymphocytes. We recently found that early activated DC (i.e. DC exposed to pro‐maturation stimuli for 8 h) were more prone to prime in vivo a type‐1 cytotoxic T cell (Tc1) response than DC exposed to pro‐maturation stimuli for 48 h (48h‐DC). We investigated whether 48h‐DC, conversely, allowed the induction of Tc2 cells. Antigen‐pulsed mouse bone‐marrow‐derived DC at any maturation stage, in the presence of exogenous IL‐12, skewed in vitro naive CD8+ T cells towards Tc1 cells, but 48h‐DC most potently, in the presence of exogenous IL‐4, favored the induction of Tc2 cells. In vivo, full maturation of DC promoted expansion of Tc2 and fall of Tc1 cells. Tc2 cells maintained a high cytolytic activity and produced significant amounts of IL‐4, IL‐5, IL‐10 and TGF‐β. Our results indicate that polarization of naive CD8+ T cells to Tc2 cells is dependent on the amount of time DC have been exposed to maturation stimuli, and might be favored in late and/or chronic phases of an immune response.