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

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Abstract

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 overview of the development of the field over the last two decades.

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Abbreviations

ACD:

Allergic contact dermatitis

ADR:

Adverse drug reaction

APC:

Antigen presenting cell

BB:

Bandrowski’s base

DC:

Dendritic cell

DNCB:

2,4-Dinitrochlorobenzene

FITC:

Fluorescein isothiocyanate

HSA:

Human serum albumin

ICS:

Intracellular cytokine staining

LC:

Langerhans cell

LLNA:

Local lymph node assay

LTT:

Lymphocyte transformation test

moDC:

Monocyte-derived dendritic cell

PBMC:

Peripheral blood mononuclear cells

PPD:

Para-phenylenediamine

TNBS:

2,4,6-Trinitrobenzene sulphonic acid

Treg:

Regulatory T cell

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Acknowledgments

We acknowledge the support for the Expert Meeting by the European Commission as part of the project “Novel Testing Strategies for In Vitro Assessment of Allergens (Sens-it-iv)”, LSHB-CT-2005-018681.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Hauptstrasse 7, 79104, Freiburg, Germany

    Stefan F. Martin & Philipp R. Esser

  2. Faculty of Biology, University of Freiburg, Freiburg, Germany

    Philipp R. Esser

  3. Miltenyi Biotec GmbH, Bergisch Gladbach, Germany

    Sonja Schmucker & Anne Richter

  4. Research Group for Immunology and Proteomics, Department of Dermatology and University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany

    Lisa Dietz & Hermann-Josef Thierse

  5. Department of Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK

    Dean J. Naisbitt & B. Kevin Park

  6. Faculté de Médecine Lyon-Sud, INSERM U851, Université de Lyon1, Lyon, France

    Marc Vocanson & Jean-Francois Nicolas

  7. Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, University Hospital and University of Bern, Bern, Switzerland

    Monika Keller & Werner J. Pichler

  8. BfR-Federal Institute for Risk Assessment, Berlin, Germany

    Matthias Peiser & Andreas Luch

  9. Institute of Molecular Biology and Bioinformatics, Charité, Berlin, Germany

    Reinhard Wanner

  10. Immunoallergology Unit, Policlinico di Careggi, Department of Internal Medicine, University of Florence, Florence, Italy

    Enrico Maggi

  11. Laboratory of Immunology, Istituto Dermopatico dell’Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy

    Andrea Cavani

  12. Department of Dermatology, VU Medical Center, Amsterdam, The Netherlands

    Thomas Rustemeyer

  13. Institute for Research in Biomedicine, Bellinzona, Switzerland

    Federica Sallusto

Authors
  1. Stefan F. Martin
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  2. Philipp R. Esser
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  3. Sonja Schmucker
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  4. Lisa Dietz
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  5. Dean J. Naisbitt
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  6. B. Kevin Park
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  7. Marc Vocanson
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  8. Jean-Francois Nicolas
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  9. Monika Keller
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  10. Werner J. Pichler
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  11. Matthias Peiser
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  12. Andreas Luch
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  13. Reinhard Wanner
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  14. Enrico Maggi
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  15. Andrea Cavani
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  16. Thomas Rustemeyer
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  17. Anne Richter
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  18. Hermann-Josef Thierse
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  19. Federica Sallusto
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Corresponding author

Correspondence to Stefan F. Martin.

Additional information

This article is dedicated to the memory of our colleague and friend Reinhard Wanner, died 2 April 2010.

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Martin, S.F., Esser, P.R., Schmucker, S. et al. T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays. Cell. Mol. Life Sci. 67, 4171–4184 (2010). https://doi.org/10.1007/s00018-010-0495-3

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  • DOI: https://doi.org/10.1007/s00018-010-0495-3

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