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

Jacques Banchereau, Lu Ann Thompson-Snipes, Sandra Zurawski, Jean Philippe Blanck, Yanying Cao, Sandra Clayton, Jean Pierre Gorvel, Gerard Zurawski, Eynav Klechevsky

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

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-10 expressed by dermal CD14+ DCs) might explain the observed functional difference. Blocking IL-15 during CD8+ T-cell priming reduced T-cell proliferation by ∼ 50%. These IL-15-deprived CD8+ T cells did not acquire the phenotype of effector memory cells. They secreted less IL-2 and IFN-γ and expressed only low amounts of CD107a, 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-10 during cocultures of dermal CD14+ DCs and naive CD8+ T cells enhanced the generation of effector CTLs, whereas addition of IL-10 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-10. Thus, the respective production of IL-15 and IL-10 explains the contrasting effects of LCs and dermal CD14+ DCs on CD8+ T-cell priming.

Original languageEnglish
Pages (from-to)5742-5749
Number of pages8
JournalBlood
Volume119
Issue number24
DOIs
StatePublished - Jun 14 2012

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