T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

Abstract

Background: There is considerable interest in understanding the immunological variables that have the greatest influence on the effectiveness of sensitization by contact allergens, particularly in the context of developing new paradigms for risk assessment of novel compounds.Objectives: To examine the relationship between patch test score for three different contact allergens and the characteristics of T cell responses.Methods: A total of 192 patients with confirmed nickel, p-phenylenediamine (PPD) or methylisothiazolinone (MI) allergy were recruited from the Contact Dermatitis Investigation Unit at Salford Royal Hospital. Severity of allergy was scored by the use of patch testing, peripheral blood lymphocytes were characterized for T cell phenotype by flow cytometry, and proliferative activity was characterized by radiolabelled thymidine incorporation. Comparisons were drawn with buffy coat samples from healthy volunteers.Results: Patch test positivity for nickel, PPD and MI was associated with changes in the phenotype of peripheral blood T cells: increases in naïve cells, decreases in regulatory T cell frequency and the CD4 + /CD8 hi ratio, and increased expression of the skin-homing marker cutaneous lymphocyte antigen (CLA), particularly for those patients with a +++ patch test score.Conclusions: This increased understanding of the characteristics of the T cell responses to contact allergens may provide parameters with which to better measure health risks associated with skin sensitization. K E Y W O R D SCD4, CD8, inverted CD4/CD8, skin-homing CLA, lymphocyte transformation test, T cell phenotype, RRID:SCR_001905

In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review

“…All chemical concentrations are listed in Table S2 (Supplementary Material) . Protein-conjugated chemicals (i.e., PPD- and MI-HSA) induced a comparable or even better proliferative response compared to the soluble correspondent chemical ( Supplementary Material, Table S2 ) (Jenkinson, 2010; Oakes, 2017; Popple, 2016; Wicks, 2019) [ 79 , 100 , 102 , 116 ]. Jenkinson and colleagues (2010) [ 79 ] calculated the equivalent molar scale of soluble and HSA-associated PPD to compare the strength of induced activation/proliferation.…”

“…They revealed that HSA-bound PPD possesses a stronger antigenic capacity. In the case of the protein-bound forms of the chemicals, the induced proliferative responses follow the classical dose-dependent trend and better correlate to patients’ patch test results (Popple, 2016; Wicks, 2019) [ 102 , 116 ]. Soluble chemicals generally become toxic at higher concentrations.…”

“…Three publications explored the involvement of naïve and/or memory T cell subsets (Gibson, 2015; Kim, 2016; Li, 2019) [ 94 , 119 , 120 ]. Two publications studied cell frequencies of CD4+ and CD8+ naïve and memory T cells (Oakes, 2017; Wicks, 2019) [ 100 , 102 ].…”

“…Sieben and colleagues (2001) [ 105 ] observed that 83% of established eugenol-specific T cell clones were CD4+HLA-DR+, and the remaining 17% were CD8+. Wicks, 2019 [ 102 ] and Oakes, 2017 [ 100 ] both observed a shift from the central memory (CM) to the effector memory (EM) compartment in PPD and PPD-HSA stimulated CD4+ and CD8+ T cells of allergic patients. Additionally, in the former study, an expansion of naïve T cells was detected in the blood compartment.…”

“…Additionally, in the former study, an expansion of naïve T cells was detected in the blood compartment. A simultaneous contraction of the memory T cell population (probably due to recruitment to the site of patch test application) was also observed [ 102 ].…”