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Jeanne Kehren^*, Cyril Desvignes, Maya Krasteva^*, Marie-Thérèse Ducluzeau^*, Olga Assossou^*, Françoise Horand^*, Michael Hahne, David Kägi^||, Dominique Kaiserlian, and Jean-François Nicolas^*,¶

From the ^* Institut National de la Santé et de la Recherche Médicale (INSERM) U503, Faculté Laennec, F-69372 Lyon Cedex 08, France; INSERM U404, F-69365 Lyon Cedex 07, France; the Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, France; the ^|| Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada; and the ^¶ Department of Clinical Immunology, Centre Hospitalier Lyon-Sud, F-69495 Pierre-Benite, France

Contact hypersensitivity (CHS) is a T cell–mediated skin inflammation induced by epicutaneous exposure to haptens in sensitized individuals. We have previously reported that CHS to dinitrofluorobenzene in mice is mediated by major histocompatibility complex (MHC) class I–restricted CD8⁺ T cells. In this study, we show that CD8⁺ T cells mediate the skin inflammation through their cytotoxic activity. The contribution of specific cytotoxic T lymphocytes (CTLs) to the CHS reaction was examined both in vivo and in vitro, using mice deficient in perforin and/or Fas/Fas ligand (FasL) pathways involved in cytotoxicity. Mice double deficient in perforin and FasL were able to develop hapten-specific CD8⁺ T cells in the lymphoid organs but did not show CHS reaction. However, they did not generate hapten-specific CTLs, demonstrating that the CHS reaction is dependent on cytotoxic activity. In contrast, Fas-deficient lpr mice, FasL-deficient gld mice, and perforin-deficient mice developed a normal CHS reaction and were able to generate hapten-specific CTLs, suggesting that CHS requires either the Fas/FasL or the perforin pathway. This was confirmed by in vitro studies showing that the hapten-specific CTL activity was exclusively mediated by MHC class I–restricted CD8⁺ T cells which could use either the perforin or the Fas/FasL pathway for their lytic activity. Thus, cytotoxic CD8⁺ T cells, commonly implicated in the host defence against tumors and viral infections, could also mediate harmful delayed-type hypersensitivity reactions.

Key Words: cytotoxic T lymphocyte • contact hypersensitivity • contact dermatitis • hapten • dinitrofluorobenzene • CD8⁺ T cells

Abbreviations used: CHS, contact hypersensitivity; DNBS, dinitrobenzene sulfonic acid; DNFB, dinitrofluorobenzene; DTH, delayed-type hypersensitivity; ELISPOT, enzyme-linked immunospot; HPRT, hypoxanthine phosphoribosyltransferase; I^0/0, MHC class I–deficient; II^0/0, MHC class II–deficient; P^0/0, perforin-deficient; LC, Langerhans cell; SFC, spot-forming cell.

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