The Cooperative Role of CD326+ and CD11b+ Dendritic Cell Subsets for a Hapten-Induced Th2 Differentiation

Abstract

Dendritic cells (DCs) play a critical role in directing immune responses. Previous studies have identified a variety of DC subsets and elucidated their context-dependent functions that parallel those of effector Th cell subsets. However, little is known about the DC subsets responsible for differentiation of Th2 cells governing allergic contact dermatitis. In this study, we sought to determine the DC subset(s) that mediate Th2 priming in hapten-sensitized mice. We induced hapten-specific Th2 differentiation by sensitizing the mice with a single application of FITC dissolved in acetone:dibutyl phthalate, and traced the immune cells responsible for inducing the Th2 differentiation process at the primary stimulation, enabling us to track Th2 priming in vivo and to delete basophils and specific DC subsets. Our analysis revealed that IL-4 was produced in vivo as early as day 3 from CD4⁺ T cells with a single application of FITC. Basophils, despite producing IL-4 1 d earlier than T cells, were found to be dispensable for Th2 differentiation. Instead, we demonstrated that CD326⁺ dermal DCs and Langerhans cells were redundantly required for FITC-induced Th2 differentiation in vivo. Moreover, the cooperation of CD326⁺ Langerhans cells and CD11b⁺ DCs differentiated naive T cells into Th2 cells in vitro. Collectively, our findings highlight at least two DC subsets that play a critical role in polarizing naive CD4⁺ T cells to Th2 cells and support a two-hit model for Th2 differentiation.