Chemokine responses distinguish chemical-induced allergic from irritant skin inflammation: Memory T cells make the difference

CXCL9 and CXCL10 are selectively upregulated in hapten-specific but not in irritant contact dermatitis. A, Ear-swelling responses (mm × 10⁻²) after epicutaneous application of either vehicle, the standard irritant croton oil or the hapten DNFB. Quantitative real-time PCR analysis of CXCL9 (B), CXCL10 (C), and CCL20 (D) at indicated time points in epidermal sheets. E, Ear-swelling responses (mm × 10⁻²) of nickel-sensitized mice 48 hours after intradermal challenge with NiCl₂ or saline. Quantitative real-time PCR analysis of CXCL9 (F) and CXCL10 (G) in epidermal sheets of nickel-specific allergic contact dermatitis and controls. Values are expressed as femtograms of target gene in 12.5 ng of total cDNA.

Quantitative real-time PCR analysis of CXCL9 (A), CXCL10 (B), CXCL11 (C), and CCL20 (D) expression in skin specimens obtained from NiSO₄ and SLS patch tests of nickel-sensitized patients (n = 8) at 0, 2, 6, and 48 hours after chemical exposure, respectively. Values are expressed as femtograms of target gene in 25 ng of total cDNA.

Shrunken centroids ranking chemokine expression in human skin specimens of NiSO₄ or SLS patch tests of Ni-sensitized patients (n = 8). Horizontal values represent log ratios of gene expression.

Immunhistochemical evaluation of CXCL9 (A-F), CXCL10 (G-L), and CXCL12 (M-R) expression in human skin specimens of NiSO₄ patch tests versus SLS patch tests.

Quantitative real-time PCR analysis of CXCL9, CXCL10, CXCL11 , and CCL20 expression in resting and activated structural cells of the skin (A-D: representative results from single donors) as well as Langerhans-type and interstitial-type dendritic cells (E-H; mean + SD of 2 independent donors). Quantitative real-time PCR analysis of CD25 (I) and IFN-γ (J) expression in DNP-specific human T-cell clones stimulated with PHA or with their relevant antigen DNP. Results are representative of 2 individual experiments with 2 different donors. Values are expressed as femtograms of target gene in 12.5 ng of total cDNA.

Migratory response toward CXCL10 of CD4⁺CLA⁺ T cells (A) or CD8⁺CLA⁺ T cells (B) in the presence or absence of a suboptimal dose of CXCL12 (10 ng/mL). Dose response of CD4⁺CLA⁺ T cells (C) or CD8⁺CLA⁺ T cells (D) to CCL27 in the presence or absence of a suboptimal dose of CXCL12 (10 ng/mL). Migratory response of CD4⁺CLA⁺ T cells (E) or CD8⁺CLA⁺ T cells (F) to a suboptimal dose of CXCL12 after priming with CXCL10. Results of triplicate experiments are shown. G, Ear-swelling responses after adoptive transfer of spleen and lymph node cells from DNFB-sensitized mice. Before adoptive transfer cells were exposed to 1 μg/mL CXCL10 or saline. Ear-swelling response was measured 24, 48, and 72 hours after adoptive transfer. For statistical analysis, a Student t test was performed. ∗P < .05; ∗∗∗P < .005.