Skin inflammation during contact hypersensitivity is mediated by early recruitment of CD8+ T cytotoxic 1 cells inducing keratinocyte apoptosis.
Contact hypersensitivity (CHS) is a T cell-mediated, Ag-specific skin inflammation induced by skin exposure to haptens in sensitized individuals. Th1/T cytotoxic 1 cells are effector cells of CHS, whereas Th2/T regulatory CD4(+) T cells have down-regulating properties. We have previously shown that CHS to 2,4-dinitrofluorobenzene is mediated by specific CD8(+) effector cells, whose cytolytic activity is mandatory for induction of skin inflammation. In this study, using immunohistochemistry and RT-PCR analysis, we show that CD8(+) T cells are rapidly recruited into the skin at the site of hapten challenge before the onset of clinical and histological signs of skin inflammation. This early CD8(+) T cell recruitment is concomitant with: 1) transient IFN-gamma mRNA expression suggesting local activation of effector cells; and 2) induction of keratinocyte (KC) apoptosis which gradually increased to a maximum at the peak of the CHS response. Alternatively, skin infiltration of CD4(+) T cells occurred later and coincided with the peak of the CHS reaction and the beginning of the resolution of skin inflammation. Mice deficient in CD8(+) T cells did not develop CHS, whereas mice deficient in CD4(+) T cells developed an enhanced inflammatory response with increased numbers of CD8(+) T cells recruited in the skin associated with massive KC apoptosis. These data show that CHS is due to the early and selective recruitment in the skin of CD8(+) T cytotoxic 1 effector cells responsible for KC apoptosis.
Akiba
Hitoshi
H
Institut National de la Santé et de la Recherche Médicale, Unité 503 and Unité 404, Lyon, France. hakiba@fmu.ac.jp
Kehren
Jeanne
J
Ducluzeau
Marie-Thérèse
MT
Krasteva
Maya
M
Horand
Françoise
F
Kaiserlian
Dominique
D
Kaneko
Fumio
F
Nicolas
Jean-François
JF
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D004139:Dinitrofluorobenzene / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D004139:Dinitrofluorobenzene