Pathophysiology of fixed drug eruption: the role of skin-resident T cells.
OBJECTIVE
Fixed drug eruption is a distinct variant of drug-induced dermatoses characterized by their relapse in the same location after the administration of the causative drug. We have recently shown that intraepidermal CD8+ T cells phenotypically resembling effector memory T cells are greatly enriched in the resting lesions of FDE. Although effector memory T cells have been implicated as the mediators of protection in epithelial tissues, our observation raises an alternative possibility that improper, enhanced or uncontrolled activation of intraepidermal T cells could contribute to severe tissue injury. Until recently, however, their detrimental effects on epithelial tissues have rarely been examined. The focus of this review is on how intra-epidermal T cells originally evolved to protect tissue integrity can exert an opposite action that is deleterious to the host.


RESULTS
Because those T cells residing in the lesions, upon activation, can rapidly produce large amounts of IFN-gammaepsilon followed by localized epidermal injury, their activation is probably essential for the initiation of deleterious inflammatory responses in the lesions. The activity of these potent effector T cells is therefore carefully controlled to prevent unwanted tissue injury under physiological conditions. A complex interplay of stop and go signals to the skin-resident T cells provides a delicate balance between cell death and survival, thereby determining the degree and outcome of inflammation generated in response to pathogens or antigens.


CONCLUSIONS
This consideration may provide important insights into the way in which skin-resident T cells maintain immunological homeostasis in the skin.
Department of Dermatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. tpshio@kyorin-u.ac.jp
Tetsuo
T
Shiohara
Yoshiko
Y
Mizukawa
Yuichi
Y
Teraki
D003875:Drug Eruptions / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D012867:Skin / Q000098:blood supply / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology