In Vitro Priming of Naı̈ve T-cells with p-Phenylenediamine and Bandrowski's Base.
p-Phenylenediamine (PPD) is a component of hair dye formulations that is associated with T-cell mediated allergic contact dermatitis. Antigen-specific T-cells from allergic contact dermatitis patients are activated with either PPD or the oxidation product, Bandrowski's base. In nonallergic individuals, T-cells that are activated by Bandrowski's base, but not by PPD, are readily detectable. The aim of the current study was to use an in vitro T-cell priming assay to assess the activation of memory and naı̈ve T-cells from healthy donors with PPD and Bandrowski's base, and to compare these responses to those observed from allergic patients. Both PPD and Bandrowski's base-responsive clones were generated from allergic patients. The majority of Bandrowski's base-responsive clones were CD4+ and displayed a lack of PPD reactivity. In contrast, CD4+ and CD8+ clones displaying PPD reactivity were detected. Approximately 25% of these displayed low levels of reactivity to Bandrowski's base. Clones from the allergic patients secreted a range of cytokines including IFN-γ, Il-13, and Il-22. In healthy donors, Bandrowski's base-specific T-cell proliferative responses and cytokine secretion were detected with both naı̈ve and memory T-cells. T-cell clones generated from the Bandrowski's base-responsive cultures responded to Bandrowski's base but not PPD. PPD-specific naı̈ve and memory T-cell responses were not detected from healthy donors. These data show that Bandrowski's base stimulates pre-existing memory T-cells isolated from healthy donors and primes naı̈ve T-cells when the chemical is bound to autologous dendritic cells. Priming naı̈ve T-cells against PPD failed, suggesting an important individual susceptibility factor is missing from the in vitro T-cell priming assay.
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool , Ashton Street, Liverpool L69 3GE, U.K.
Andrew
A
Gibson
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool , Ashton Street, Liverpool L69 3GE, U.K.|Department of Allergy and Clinical Immunology, Ajou University School of Medicine , Suwon, South Korea.
Seung-Hyun
SH
Kim
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool , Ashton Street, Liverpool L69 3GE, U.K.
Lee
L
Faulkner
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool , Ashton Street, Liverpool L69 3GE, U.K.
Jane
J
Evely
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool , Ashton Street, Liverpool L69 3GE, U.K.
Munir
M
Pirmohamed
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool , Ashton Street, Liverpool L69 3GE, U.K.
Kevin B
KB
Park
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool , Ashton Street, Liverpool L69 3GE, U.K.
Dean J
DJ
Naisbitt
D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000378:metabolism / Q000473:pathology*; D006202:Hair Dyes / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010084:Oxidation-Reduction; D010655:Phenylenediamines / Q000737:chemistry / Q000633:toxicity*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000097043:Interleukin-22
D006202:Hair Dyes; D007371:Interferon-gamma; D018793:Interleukin-13; D007378:Interleukins; D010655:Phenylenediamines; D000097043:Interleukin-22; C051597:Bandrowski's base; C029728:4-phenylenediamine