J. Exp. Med., Volume 189, Number 5, March 1, 1999 779-786

Cytotoxicity Is Mandatory for CD8⁺ T Cell-mediated Contact Hypersensitivity

By 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.

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