Cytotoxicity is mandatory for CD8(+) T cell-mediated contact hypersensitivity.
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.
Institut National de la Santé et de la Recherche Médicale (INSERM) U503, Faculté Laennec, F-69372 Lyon Cedex 08, France.
J
J
Kehren
C
C
Desvignes
M
M
Krasteva
M T
MT
Ducluzeau
O
O
Assossou
F
F
Horand
M
M
Hahne
D
D
Kägi
D
D
Kaiserlian
J F
JF
Nicolas
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D003602:Cytotoxicity, Immunologic; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D053222:Fas Ligand Protein; D006241:Haptens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008221:Lymphoid Tissue / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012867:Skin / Q000276:immunology; D019014:fas Receptor / Q000235:genetics
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006241:Haptens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene