Skin Exposure to Weak and Moderate Contact Allergens Induces IFNγ Production by Lymph Node Cells of CD4+ T-Cell-Depleted Mice

Vocanson, Marc; Hennino, Anà; Rozières, Aurore; Cluzel-Tailhardat, Magalie; Poyet, Gaelle; Valeyrie, Magalie; Bénetière, Josette; Tédone, R.; Kaiserlian, Dominique; Nicolas, Jean‐François

doi:10.1038/jid.2008.352

Cited by 20 publications

(12 citation statements)

References 20 publications

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“…The idea that immune tolerance rather than ignorance explains the general innocuity of weak haptens is supported both in mouse and human. Indeed, we showed that normal mice do not mount CHS responses to common chemical allergens of fragrance unless they are acutely depleted of Tregs (11). Moreover, studies of nickel allergy best illustrated that a weak sensitizing allergen can activate Tregs, as most healthy control individuals harbor functional allergen-specific and suppressive CD4 + CD25 + Tregs (12).…”

Section: Introductionmentioning

confidence: 99%

“…Increasing evidence indicates that CD4 + CD25 + Foxp3 + Tregs are essential to controlling the development and severity of skin allergy in both mouse models (5,8) and in humans (12). Indeed, allergen-specific Tregs can be detected in allergen-exposed but nonallergic individuals (12) and are likely mandatory for prevention of sensitization, as depletion of Tregs in mouse models allows for development of CHS to otherwise nonsensitizing weak haptens (11). Yet an understanding of how allergen-specific Tregs are generated is still elusive.…”

Section: Cd207 -Ddcs To Lnsmentioning

confidence: 99%

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Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

Vocanson²,

et al. 2012

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Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8 + T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8 + T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8 + T cells and activation of a population of T cells identified as ICOS + CD4 + Foxp3 + Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.

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Section: Introductionmentioning

confidence: 99%

Section: Cd207 -Ddcs To Lnsmentioning

confidence: 99%

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

Vocanson²,

et al. 2012

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“…Depletion of regulatory CD25 + - or CD4 + -T cells in vivo increases the number of IFN-γ-producing T cells during sensitisation. Likewise the sensitivity of the corresponding in vitro assays can be increased by using systems depleted of CD25 + T cells [187, 188]. …”

Section: Introductionmentioning

confidence: 99%

Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects

Peiser

Tralau

Heidler

et al. 2011

Cell. Mol. Life Sci.

321

214

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Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German ‘Federal Institute for Risk Assessment’ hosted an ‘International Workshop on Contact Dermatitis’. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15–20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.

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“…T cells were depleted before sensitization [88][89][90]. In addition sensitive detection methods allow amplification of weak T-cell responses by polyclonal expansion of precursors [63] and the multiparametric analysis of single cells using flow cytometric detection of cell surface markers including those that indicate antigen-specific activation and intracellular cytokines [51,[56][57][58].…”

Section: Resultsmentioning

confidence: 99%

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Martin

Esser

Schmucker

et al. 2010

Cell. Mol. Life Sci.

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133

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Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an This article is dedicated to the memory of our colleague and friend Reinhard Wanner, died 2 April 2010. Cellular and Molecular Life Sciences overview of the development of the field over the last two decades.

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Skin Exposure to Weak and Moderate Contact Allergens Induces IFNγ Production by Lymph Node Cells of CD4+ T-Cell-Depleted Mice

Cited by 20 publications

References 20 publications

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

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