Thymic stromal lymphopoietin (TSLP) endows human blood-derived CD11c(+) dendritic cells (DCs) and Langerhans cells (LCs) obtained from human epidermis with the capacity to induce pro-allergic T cells. In this study, we investigated the effect of TSLP on umbilical cord blood CD34(+) -derived LC-like cells. These cells are often used as model cells for LCs obtained from epidermis. Under the influence of TSLP, both cell types differed in several ways. As defined by CD83, CD80 and CD86, TSLP did not increase maturation of LC-like cells when compared with freshly isolated LCs and epidermal émigrés. Differences were also found in the production of chemokine (C-C motif) ligand (CCL)17. LCs made this chemokine only when primed by TSLP and further stimulated by CD40 ligation. In contrast, LC-like cells released CCL17 in response to CD40 ligation, irrespective of a prior treatment with TSLP. Moreover, the CCL17 levels secreted by LC-like cells were at least five times higher than those from migratory LCs. After maturation with a cytokine cocktail consisting of tumour necrosis factor-α, interleukin (IL)-1β, IL-6 and prostaglandin (PG)E(2) LC-like cells released IL-12p70 in response to CD40 ligation. Most importantly and in contrast to LC, TSLP-treated LC-like cells did not induce a pro-allergic cytokine pattern in helper T cells. Due to their different cytokine secretion and the different cytokine production they induce in naïve T cells, we conclude that one has to be cautious to take LC-like cells as a paradigm for 'real' LCs from the epidermis.