Oral prednisone regulates human skin T cells in delayed-type hypersensitivity reaction elicited by diphencyprone

Abstract

Background: The potential benefit of inducing delayed-type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders was recently reported using bulk molecular technologies. Immunophenotype of skin T cells, including cellular source of Type 1, 2, and 3 cytokines, in a local DTH reaction and their modulation by oral drugs remain to be investigated.

Method: Purified protein derivative (PPD), nickel, diphencyprone (DPCP), or house dust mite (HDM) was administered as sensitizer to 40 HVs. In addition, 20 HVs were randomized to receive oral prednisone or placebo before DPCP challenge. We characterized the immunophenotype and cytokine profile of CD3⁺ T cell infiltrate, and examined the modulation by oral prednisone at single-cell level using multiparameter flow cytometry and unsupervised analysis.

Results: PPD was biased toward a Th1 and Tc1 response, and HDM a Th2/Th17 and Tc2. Nickel and DPCP displayed a mixed Th1/Th2/Th17 and Tc1 response. CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells (Tregs), the minor CD4⁺ CD25⁺ FoxP3^- ICOS⁺ PD-1⁺ (activated PD-1⁺ Th), and CD103⁺ tissue resident memory (TRM) cells were detected in all groups. DPCP uniquely elicited rare CD8⁺ CD103⁺ CD25⁺ RoRγt⁺ PD-1⁺ ICOS⁺ IFNγ⁺ T cells (activated CD8⁺ IFNγ⁺ PD-1⁺ TRM). Oral prednisone decreased frequencies of activated PD-1⁺ Th and CD8⁺ IFNγ⁺ PD-1⁺ TRM subsets relative to placebo in DPCP reaction. The latter was positively correlated with improvement of clinical parameters with prednisone.

Conclusion: DTH and skin CD3⁺ T cell profiles elicited by common sensitizers can be modulated by oral drugs. Corticosteroids reduce the frequencies of activated PD-1⁺ Th and CD8⁺ IFNγ⁺ PD-1⁺ TRM cells after DPCP exposure.

Keywords: DPCP; delayed-type hypersensitivity; flow cytometry; skin T cells; systemic prednisone.