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The differential production of cytokines by human Langerhans cells and dermal CD14(+) DCs controls CTL priming

, : The differential production of cytokines by human Langerhans cells and dermal CD14(+) DCs controls CTL priming. Blood 119(24): 5742-5749

We recently reported that human epidermal Langerhans cells (LCs) are more efficient than dermal CD14+ DCs at priming naive CD8+ T cells into potent CTLs. We hypothesized that distinctive dendritic cell (DC) cytokine expression profiles (ie, IL-15 produced by LCs and IL-1 expressed by dermal CD14+ DCs) might explain the observed functional difference. Blocking IL-15 during CD8+ T-cell priming reduced T-cell proliferation by ~ 5%. These IL-15–deprived CD8+ T cells did not acquire the phenotype of effector memory cells. They secreted less IL-2 and IFN- and expressed only low amounts of CD17a, granzymes and perforin, and reduced levels of the antiapoptotic protein Bcl-2. Confocal microscopy analysis showed that IL-15 is localized at the immunologic synapse of LCs and naive CD8+ T cells. Conversely, blocking IL-1 during cocultures of dermal CD14+ DCs and naive CD8+ T cells enhanced the generation of effector CTLs, whereas addition of IL-1 to cultures of LCs and naive CD8+ T cells inhibited their induction. TGF-β1 that is transcribed by dermal CD14+ DCs further enhanced the inhibitory effect of IL-Thus, the respective production of IL-15 and IL-1 explains the contrasting effects of LCs and dermal CD14+ DCs on CD8+ T-cell priming.


PMID: 22535664

DOI: 10.1182/blood-2011-08-371245

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