Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. It is used as an immune-modulating therapeutic, but its molecular effects in human skin are largely unknown. We studied cellular and molecular characteristics of a recall response to 0.04% DPCP at 3-day (peak) and 14-day (resolution) time points using immune markers, reverse-transcriptase–PCR (RT–PCR), and gene array approaches. A peak response showed modulation of ∼7,500 mRNA transcripts, with high expression of cytokines that define all major effector T-cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC) infiltrates were measured. The resolution reaction was characterized by unexpectedly high levels of T cells and mature (DC-lysosome-associated membrane glycoprotein positive (DC-LAMP+)) DCs, but with marked decreases in expression of IL-2, IFNγ, and other T cell–derived cytokines. However, negative immune regulators such as IDO1 that were high in peak reactions, continued to have high expression in resolution reactions. In the resolution reaction, ∼1,500 mRNA transcripts were significantly different from placebo-treated skin. These data suggest that the response to DPCP evolves from an inflammatory/effector peak at day 3 to a more regulated immune response after 14 days. This model system could be useful for further dissection of mechanisms of immune activation or negative immune regulation in human skin.

As imiquimod, like DPCP, acts through the immune system, we elected to perform a biopsy of imiquimod-treated skin, so that we could compare it to a biopsy of DPCP-treated skin from the same patient. This revealed increases in various immune cell types in DPCP-treated compared to imiquimod-treated skin, including: CD3+ T cells, CD8+ cytotoxic T cells, CD11c+ myeloid dendritic cells, and CD163+ macrophages (Figure 6.8). Furthermore, by qRT-PCR analysis, DPCP induced stronger upregulation of IFNγ (3-fold) and IL-9 (5-fold) than imiquimod.