In vitro treatment of human transforming growth factor-β1-treated monocyte-derived dendritic cells with haptens can induce the phenotypic and functional changes similar to epidermal Langerhans cells in the initiation phase of allergic contact sensitivity

Abstract

Human monocyte-derived dendritic cells (MoDCs) obtained from peripheral blood monocytes (PBMC) cultured with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) can be activated in vitro by a variety of simple chemicals such as haptens and several metals. Recently, it has been demonstrated that transforming growth factor-β₁ (TGF-β₁) can induce further differentiation of MoDCs to the cells that share some characteristics with epidermal Langerhans cells, i.e. they contain Birbeck granules and express E-cadherin. In this study, using such TGF-β₁-treated dendritic cells (TGF-β₁⁺ DCs), we examined the in vitro effects of representative haptens, i.e. NiCl₂ and dinitrochlorobenzene (DNCB), on their phenotypic and functional characteristics, comparing with those reported in vivo in epidermal Langerhans cells during the sensitization phase of a contact sensitivity reaction. Treatment of TGF-β₁⁺ DCs with NiCl₂ increased their expression of the molecules related to antigen presentation such as CD86, major histocompatibility complex class I and class II, and CD83, although weakly, in addition to that of those essential for their migration to the regional lymph nodes, such as CD49e, CD44 and its variant 6, while it down-regulated the expression of the molecules required for homing to the skin and staying in the epidermis, such as cutaneous leucocyte antigen (CLA) and E-cadherin. It also increased the production of tumour necrosis factor-α, but not that of IL-1β or IL-12. DNCB also increased their CD86 expression and down-regulated E-cadherin and CLA, but did not affect other phenotypic changes that were observed in TGF-β₁⁺ DCs treated with NiCl₂. TGF-β₁⁺ DCs treated with either NiCl₂ or DNCB increased their allogeneic T-cell stimulatory function. In addition, reverse transcribed polymerase chain reaction revealed augmented expression of chemokine receptor 7 mRNA by TGF-β₁⁺ DCs when treated with either NiCl₂ or DNCB. Moreover, consistent with this data, TGF-β₁⁺ DCs treated with these chemicals chemotactically responded to macrophage inflammatory protein-3β. These data suggest the possibility that TGF-β₁⁺ DCs present a good in vitro model to study the biology of epidermal Langerhans cells.