Delayed-type hypersensitivity reaction to paraphenylenediamine is mediated by 2 different pathways of antigen recognition by specific alphabeta human T-cell clones

J Allergy Clin Immunol. 2002 Jun;109(6):1005-11. doi: 10.1067/mai.2002.123872.


Background: Allergic contact dermatitis to paraphenylenediamine (PPD) is a frequent cause of morbidity and occupational disability.

Objective: The aim of the study was to characterize T-cell responses to PPD and Bandrowski's base (BB), an autoxidation product of PPD, by using polyclonal and monoclonal T-lymphocyte cultures.

Methods: PPD- and BB-driven proliferation of PBMCs and T-cell clones (TCCs) was assessed by means of tritiated thymidine incorporation. Surface markers were studied by means of flow cytometry, and cytokine generation was assessed with an ELISA.

Results: TCCs, with one exception, were CD4+/CD45RO+, and T-cell receptors were alphabeta+. Three of 6 TCCs expressed Vbeta 16. TCC stimulation was HLA-DP restricted, and TCCs secreted IL-4, IL-5, and marginal levels of IFN-gamma. TCCs reacted to both PPD and BB. Presentation of BB to TCCs was dependent on viable antigen-presenting cells (APCs) pulsed for 4 hours, and fixed APCs failed to stimulate TCCs. Moreover, polyclonal responses to BB were enhanced by metabolically active enzymes, such as cytochrome P450 enzymes. BB has to be metabolized and processed. In contrast, fixation of APCs did not impair their ability to present PPD to TCC, whereas pulsing of APCs with PPD failed to stimulate TCCs. Thus PPD had to be present during the process, and polyclonal stimulation was not enhanced by cytochromes.

Conclusion: These results suggest that PPD itself can be recognized by T cells through a processing-independent pathway, whereas its autoxidation product, BB, required processing and possibly metabolism to stimulate the same TCC. Our data demonstrate that 2 distinct pathways of antigen presentation to activate specific TCCs are involved in the immune response to PPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology
  • Cells, Cultured
  • Clone Cells
  • Dermatitis, Allergic Contact / etiology*
  • Dermatitis, Allergic Contact / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HLA-DP Antigens / metabolism
  • Humans
  • Hypersensitivity, Delayed / chemically induced*
  • Hypersensitivity, Delayed / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Male
  • Occupational Diseases / etiology*
  • Occupational Diseases / immunology
  • Phenylenediamines / adverse effects*
  • Receptors, Antigen, T-Cell, alpha-beta / drug effects
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • HLA-DP Antigens
  • Interleukin-5
  • Phenylenediamines
  • Receptors, Antigen, T-Cell, alpha-beta
  • Bandrowski's base
  • Interleukin-4
  • Interferon-gamma
  • 4-phenylenediamine