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Cellular and Molecular Life Sciences

, Volume 67, Issue 24, pp 4171–4184 | Cite as

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

  • Stefan F. Martin
  • Philipp R. Esser
  • Sonja Schmucker
  • Lisa Dietz
  • Dean J. Naisbitt
  • B. Kevin Park
  • Marc Vocanson
  • Jean-Francois Nicolas
  • Monika Keller
  • Werner J. Pichler
  • Matthias Peiser
  • Andreas Luch
  • Reinhard Wanner
  • Enrico Maggi
  • Andrea Cavani
  • Thomas Rustemeyer
  • Anne Richter
  • Hermann-Josef Thierse
  • Federica Sallusto
Review

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.

Keywords

Allergy Contact dermatitis Drug hypersensitivity T cell Immunotoxicology In vitro alternatives Non-animal testing Bioassay 

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

Notes

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.

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Stefan F. Martin
    • 1
  • Philipp R. Esser
    • 1
    • 2
  • Sonja Schmucker
    • 3
  • Lisa Dietz
    • 4
  • Dean J. Naisbitt
    • 5
  • B. Kevin Park
    • 5
  • Marc Vocanson
    • 6
  • Jean-Francois Nicolas
    • 6
  • Monika Keller
    • 7
  • Werner J. Pichler
    • 7
  • Matthias Peiser
    • 8
  • Andreas Luch
    • 8
  • Reinhard Wanner
    • 9
  • Enrico Maggi
    • 10
  • Andrea Cavani
    • 11
  • Thomas Rustemeyer
    • 12
  • Anne Richter
    • 3
  • Hermann-Josef Thierse
    • 4
  • Federica Sallusto
    • 13
  1. 1.Allergy Research Group, Department of DermatologyUniversity Medical Center FreiburgFreiburgGermany
  2. 2.Faculty of BiologyUniversity of FreiburgFreiburgGermany
  3. 3.Miltenyi Biotec GmbHBergisch GladbachGermany
  4. 4.Research Group for Immunology and Proteomics, Department of Dermatology and University Medical Center MannheimUniversity of HeidelbergMannheimGermany
  5. 5.Department of Pharmacology, MRC Centre for Drug Safety ScienceUniversity of LiverpoolLiverpoolUK
  6. 6.Faculté de Médecine Lyon-Sud, INSERM U851Université de Lyon1LyonFrance
  7. 7.Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, InselspitalUniversity Hospital and University of BernBernSwitzerland
  8. 8.BfR-Federal Institute for Risk AssessmentBerlinGermany
  9. 9.Institute of Molecular Biology and BioinformaticsCharitéBerlinGermany
  10. 10.Immunoallergology Unit, Policlinico di Careggi, Department of Internal MedicineUniversity of FlorenceFlorenceItaly
  11. 11.Laboratory of ImmunologyIstituto Dermopatico dell’Immacolata-Istituto di Ricovero e Cura a Carattere ScientificoRomeItaly
  12. 12.Department of DermatologyVU Medical CenterAmsterdamThe Netherlands
  13. 13.Institute for Research in BiomedicineBellinzonaSwitzerland

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