In vitro treatment of human transforming growth factor-beta(1)-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 reaction

Human monocyte-derived dendritic cells (MoDCs) obtained from peripheral blo od monocytes (PBMC) cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) can be activated in vitro by a va riety of simple chemicals such as haptens and several metals. Recently, it has been demonstrated that transforming growth factor-beta(1) (TGF-beta(1)) can induce further differentiation of MoDCs to the cells that share some c haracteristics with epidermal Langerhans cells, i.e. they contain Birbeck g ranules and express E-cadherin. In this study, using such TGF-beta(1)-treat ed dendritic cells (TGF-beta(1)(+) DCs), we examined the in vitro effects o f representative haptens, i.e. NiCl2 and dinitrochlorobenzene (DNCB), on th eir phenotypic and functional characteristics, comparing with those reporte d in vivo in epidermal Langerhans cells during the sensitization phase of a contact sensitivity reaction. Treatment of TGF-beta(1)(+) DCs with NiCl2 i ncreased their expression of the molecules related to antigen presentation such as CD86, major histocompatibility complex class I and class II, and CD 83, although weakly, in addition to that of those essential for their migra tion to the regional lymph nodes, such as CD49e, CD44 and its variant 6, wh ile it down-regulated the expression of the molecules required for homing t o the skin and staying in the epidermis, such as cutaneous leucocyte antige n (CLA) and E-cadherin. It also increased the production of tumour necrosis factor-alpha, but not that of IL-1 beta or IL-12. DNCB also increased thei r CD86 expression and down-regulated E-cadherin and CLA, but did not affect other phenotypic changes that were observed in TGF-beta(1)(+) DCs treated with NiCl2. TGF-beta(1)(+) DCs treated with either NiCl2 or DNCB increased their allogeneic T-cell stimulatory function. In addition, reverse transcri bed polymerase chain reaction revealed augmented expression of chemokine re ceptor 7 mRNA by TGF-beta(1)(+) DCs when treated with either NiCl2 or DNCB. Moreover, consistent with this data, TGF-beta(1)(+) DCs treated with these chemicals chemotactically responded to macrophage inflammatory protein-3 b eta. These data suggest the possibility that TGF-beta(1)(+) DCs present a g ood in vitro model to study the biology of epidermal Langerhans cells.