Characterization of the T cell response in allergic contact dermatitis caused by corticosteroids
Corresponding Author
Marie Baeck
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Marie Baeck, Department of Dermatology, Cliniques Universitaires Saint-Luc, U.C.L., Avenue Hippocrate 10, B-1200 Brussels, Belgium. Tel: +32 2 764 14 72; Fax: +32 2 764 80 27. E-mail: [email protected]Search for more papers by this authorAngèle Soria
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorLiliane Marot
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorIvan Theate
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorEmilie Hendrickx
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorAstrid Van Belle
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorAn Goossens
Department of Dermatology, University Hospital, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Search for more papers by this authorDominique Tennstedt
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorClaire Dachelet
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorJohnathan Jaeger
Department of Statistics, SMCS, IMMAQ Institute of Multidisciplinary Research for Quantitative Modelling and Analysis, Université Catholique de Louvain, 1348 Louvain-La-Neuve, Belgium
Search for more papers by this authorCharles Pilette
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Department of Pneumology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorJean-Christophe Renauld
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorNicolas Van Baren
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorAurore Rozières
Department of Immuno-Allergology, University Hospital Centre Lyon Sud, Hospices Civiles de Lyon, 69495 Pierre-Benite, France
Search for more papers by this authorJean-Fançois Nicolas
Department of Immuno-Allergology, University Hospital Centre Lyon Sud, Hospices Civiles de Lyon, 69495 Pierre-Benite, France
Search for more papers by this authorLaure Dumoutier
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorCorresponding Author
Marie Baeck
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Marie Baeck, Department of Dermatology, Cliniques Universitaires Saint-Luc, U.C.L., Avenue Hippocrate 10, B-1200 Brussels, Belgium. Tel: +32 2 764 14 72; Fax: +32 2 764 80 27. E-mail: [email protected]Search for more papers by this authorAngèle Soria
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorLiliane Marot
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorIvan Theate
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorEmilie Hendrickx
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorAstrid Van Belle
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorAn Goossens
Department of Dermatology, University Hospital, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Search for more papers by this authorDominique Tennstedt
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorClaire Dachelet
Department of Dermatology, Cliniques Universitaires Saint-Luc, Universite’ Catholique de Louvain, 1200 Brussels, Belgium
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorJohnathan Jaeger
Department of Statistics, SMCS, IMMAQ Institute of Multidisciplinary Research for Quantitative Modelling and Analysis, Université Catholique de Louvain, 1348 Louvain-La-Neuve, Belgium
Search for more papers by this authorCharles Pilette
Pôle Pneumologie, ORL et Dermatologie Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Department of Pneumology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
Search for more papers by this authorJean-Christophe Renauld
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorNicolas Van Baren
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorAurore Rozières
Department of Immuno-Allergology, University Hospital Centre Lyon Sud, Hospices Civiles de Lyon, 69495 Pierre-Benite, France
Search for more papers by this authorJean-Fançois Nicolas
Department of Immuno-Allergology, University Hospital Centre Lyon Sud, Hospices Civiles de Lyon, 69495 Pierre-Benite, France
Search for more papers by this authorLaure Dumoutier
Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium
de Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
Search for more papers by this authorConflicts of interest: The authors have declared no conflicts.
Summary
Background Delayed allergic hypersensitivity reactions have classically been described as type IV reactions, which are caused by T cells; however, the respective roles of CD4+ and CD8+ cells are yet to be defined. A central role for CD8+ cytotoxic T cells as effector cells has been suggested.
Objectives To determine the type of T cell involved in corticosteroid allergy.
Methods We analysed the kinetics of T cell recruitment and the cytokine production profile in positive patch tests of 27 corticosteroid-sensitized patients, as compared with control sites and control subjects. Skin biopsies, collected at 8, 24 and 48 hr following drug application, were embedded in paraffin for histological and immunohistological staining, and, in some cases, also deep-frozen for gene expression analyses.
Results CD3+ T cells were rapidly recruited in concert with the positivity of the patch test sites. High levels of interleukin (IL)-4, IL-5 and, to a lesser extent, interferon-γ suggested that both Th2 and Th1 cytokines were implicated. IL-4 was also produced by γδ T cell receptor (TCR) lymphocytes.
Conclusions This study showed that, in allergic contact dermatitis caused by corticosteroids, the inflammatory infiltrate is composed of CD3+ T cells with a predominant Th2 cytokine profile, among which IL-4 is also produced by γδ TCR lymphocytes.
References
- 1 Baeck M, Marot L, Nicolas J F, Pilette C, Tennstedt D, Goossens A. Allergic hypersensitivity to topical and systemic corticosteroids: a review Allergy 2009: 64: 978–994.
- 2 Coombs R R A, Geel P G H. Classification of allergic reactions for clinical hypersensitivity and disease In: Clinical Aspects of Immunology, 3rd edition, P G H Gell, R R A Coombs, R Lachman (eds): London, Oxford, Blackwell Scientific, 1975: pp. 761–781.
- 3 Pichler W J. Delayed drug hypersensitivity reactions Ann Intern Med 2003: 139: 683–693.
- 4 Posadas S J, Pichler W J. Delayed drug hypersensitivity reactions –new concepts Clin Exp Allergy 2007: 37: 989–999.
- 5 Peiser M, Tralau T, Heidler J et al. Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects Cell Mol Life Sci 212: 763–781.
- 6 Martins L E, Reis V M. Immunopathology of allergic contact dermatitis An Bras Dermatol 2011: 86: 419–433.
- 7 Rozières A, Vocanson M, Rodet K et al. CD8+ T cells mediate skin allergy to amoxicillin in a mouse model Allergy 2010: 65: 995–1003.
- 8 Rozières A, Hennino A, Rodet K et al. Detection and quantification of drug-specific T cells in penicillin allergy Allergy 2009: 64: 534–542.
- 9 Rozières A, Vocanson M, Said B B, Nosbaum A, Nicolas J F. Role of T cells in nonimmediate allergic drug reactions Curr Opin Allergy Clin Immunol 2009: 9: 305–310.
- 10 Vocanson M, Hennino A, Rozières A et al. Skin exposure to weak and moderate contact allergen induces IFN gamma production by lymph node cells of CD4+ T-cell-depleted mice J Invest Dermatol 2009: 129: 1185–1191.
- 11 Vocanson M, Hennino A, Cluzel-Tailhardat M et al. CD8+ T cells are effector cells of contact dermatitis to common skin allergens in mice J Invest Dermatol 2006: 126: 815–820.
- 12 Hennino A, Vocanson M, Toussaint Y et al. Skin-infiltrating CD8+ T cells initiate atopic dermatitis lesions J Immunol 2007: 178: 5571–5577.
- 13 Hennino A, Jean-Decoster C, Giordano-Labadie F, Debeer S, Vanbervliet B, Rozieres A. CD8+ T cells are recruited early to allergen exposure sites in atopy patch test reactions in human atopic dermatitis J Allergy Clin Immunol 2011: 127: 1064–1067.
- 14 Van Beelen A J, Teunissen M B, Kapsenberg M L, de Jong E C. Interleukin-17 in inflammatory skin disorders Curr Opin Allergy Clin Immunol 2007: 7: 374–381.
- 15 Ogawa A, Yoshizaki A, Yanaba K et al. The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity J Invest Dermatol 2010: 130: 1558–1570.
- 16 Sinigaglia F, Scheidegger D, Garotta G. Isolation and characterisation of Ni-specific T cell clones from patients with Ni-contact dermatitis J Immunol 1985: 135: 3929–3932.
- 17 Yokozeki H, Wu M H, Sumi K et al. Th2 cytokines, IgE and mast cells play a crucial role in the induction of para-phenylenediamine-induced contact hypersensitivity in mice Clin Exp Immunol 2003: 132: 385–392.
- 18 Coulter E M, Jenkinson C, Farrell J et al. Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individuals J Invest Dermatol 2010: 130: 161–174.
- 19 Czarnobilska E, Jenner B, Kaszuba-Zwoinska J, Kapusta M, Obtułowicz K, Thor P, Spiewak R. Contact allergy to nickel: patch test score correlates with IL-5, but not with IFN-gamma nickel-specific secretion by peripheral blood lymphocytes Ann Agric Environ Med 2009: 16: 37–41.
- 20 Minang J T, Areström I, Trove-Blomberg M, Lundeberg L, Ahlborg N. Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals Clin Exp Immunol 2006: 146: 417–426.
- 21 Padial A, Posadas S, Alvarez J et al. Nonimmediate reactions to corticosteroids suggest an immunological mechanism Allergy 2005: 60: 665–670.
- 22 Zhao Y, Balato A, Fishelevich R, Chapoval A, Mann D L, Gaspari A A. Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis Br J Dermatol 2009: 161: 1301–1306.
- 23 Baeck M, Chemelle J A, Terreux R, Drieghe J, Goossens A. Delayed hypersensitivity to corticosteroids in a series of 315 patients: clinical data and patch test results Contact Dermatitis 2009: 61: 163–175.
- 24 Isaksson M, Brandao F M, Bruze M, Goossens A. Recommendation to include budesonide and tixocortol pivalate in the European standard series Contact Dermatitis 2000: 43: 41–63.
- 25 Isaksson M. Corticosteroid contact allergy –the importance of late readings and testing with corticosteroids used by the patients Contact Dermatitis 2007: 56: 56–57.
- 26 Frome E L, Checkoway H. Use of Poisson regression models in estimating incidence rates and ratios Am J Epidemiol 1985: 121: 309–323.
- 27 Peduzzi P, Concato J, Kemper E, Holford T R, Feinstein A R. A simulation study of the number of events per variable in logistic regression analysis J Clin Epidemiol 1996: 49: 1373–1379.
- 28 Mimesh S, Pratt M. Allergic contact dermatitis from corticosteroids: reproducibility of patch testing and correlation with intradermal testing Dermatitis 2006: 17: 137–142.
- 29 Bircher A J, Thurlimann W, Hunziker T et al. Contact hypersensitivity to corticosteroids in routine patch test patients. A multi-centre study of the Swiss Contact Dermatitis Research Group Dermatology 1995: 191: 109–114.
- 30 Holtmeier W, Kabelitz D. Gammadelta T cells link innate and adaptative immune responses Immunol Allergy 2005: 86: 151–183.
- 31 Laggner U, Meglio P, Perera G K et al. Identification of a novel proinflammatory skin-homing V(gamma)9V(delta)2 T cell subset with a potential rôle in psoriasis J Immunol 2011: 187: 2783–2793.
- 32 Ptak W, Askenase P W. Gamma delta T cells assist alpha beta T cells in adoptive transfer of contact sensitivity J Immunol 1992: 149: 3503–3508.
- 33 Yokozeki H, Watanabe K, Igawa K, Miyazaki Y, Katayama I, Nishioka K. Gammadelta T cells assist alphabeta T cells in the adoptive transfer of contact hypersensitivity to para-phenylenediamine Clin Exp Immunol 2001: 125: 351–359.
- 34 Vocanson M, Rozières A, Hennino A et al. Inducible costimulator (ICOS) is a marker for highly suppressive antigen-specific T cells sharing features of Th17/Th1 and regulatory T cells J Allergy Clin Immunol 2010: 126: 280–289.