Antigen presentation by CD301b+ dermal dendritic cells dictates CD4+ T cell fate

Abstract

Abstract Different subsets of dendritic cells (DCs) induce different types of effector CD4T cells. Naïve mouse skin is populated with three major DC subsets, including epidermal Langerhans cells, CD103+ dermal DCs and CD301b+ dermal DCs, all of which migrate to the draining lymph nodes (dLNs). We showed previously that CD301b+DCs are required for the differentiation of antigen specific T helper type 2 (Th2) cells upon immunization with ovalbumin (OVA) and papain in the footpad. However, the mechanism by which CD301b+DCs induce Th2 differentiation is unclear. Here, we examined the role of antigen presentation by CD301b+DCs in the priming and Th2 differentiation of antigen-specific CD4T cells. As in CD301b+DC-depleted mice, mice lacking MHC class II (MHCII) specifically in CD301b+ cells (CD301bΔMHCII mice) showed significantly reduced IL-4 production from OVA-specific OT-II CD4T cells 7 days after immunization, suggesting that cognate interaction between CD301b+DCs and CD4T cells is required for the development of Th2 cells. In addition, although the overall cell cycle progression of OT-II cells was unaffected, their entry into the cell cycle was significantly delayed. In both CD301b+DC-depleted and CD301bΔMHCII mice, this reduction of OT-II cells was associated with impaired retention of OT-II cells in the dLN at much earlier timing. Furthermore, CD301b+DCs were required for retaining and activating wild-type polyclonal CD4T cells in the dLNs in an MHCII-dependent manner. These results indicate that CD301b+DCs are required for effective priming of CD4T cells and Th2 differentiation through their cognate interaction with antigen-specific CD4T cells.