Epidermal T Cells: Their Functional Role and Disease Relevance for Dermatologists

Abstract

T cells found within the epidermis in inflammatory dermatoses are generally accepted as making a major contribution to epidermal damage. On the other hand, those T cells residing in the murine epidermis are supposed to play an important role in protecting the epidermis from potentially dangerous immune reactions. Overwhelming evidence has accumulated that dendritic epidermal T cells (DETC) expressing monomorphic TCR gammadelta are responsible for the protection of epidermal structures against skin tumor, bacterial infection, and autoimmune attack. In animals congenitally lacking these gammadelta+ DETC, the epidermis is populated with bone marrow-derived TCR alphabeta+, CD8+ DETC. Although it remains unclear whether this subset of DETC could home to the epidermis to substitute for the physiologic function of gammadelta+ DETC or whether they would be pathologically relevant to epidermal injury, it should be noted that this subset represents the major fraction of T cells present in normal human epidermis and the most abundant in the lesional epidermis of fixed drug eruption (FDE). Because they are shown to kill target cells including keratinocytes upon stimulation and utilize a very limited range of TCR V alpha and Vbeta gene families, localized epidermal injury in FDE lesions would be mediated by activation of these epidermal T cells with autoaggressive potential. Epidermal T cells are thus likely to form several T-cell populations with different immunologic functions that are triggered by different modes of stimulation. Immune homeostasis in the epidermis would rely on a delicate balance between at least two types of epidermal T cells: autoaggressive T cells and protective T cells.

Fixed Drug Eruption Presenting as Erythema dyschromicum perstans: A Flare without Taking Any Medications

“…Although the mechanism of FDE remains unknown, there is mounting evidence to suggest that in FDE lesions localized epidermal injury is mediated by local activation of T cells residing in the lesional epidermis [8, 10, 11]. Previous immunohistochemical studies have demonstrated the existence of significant numbers of CD8+ intraepidermal T cells in the FDE lesions [10, 11], as it was also shown in this case.…”

“…Second, various nonspecific stimuli that can activate CD8+ intraepidermal T cells residing in the FDE lesions may have contributed to the flare. In this regard, we have demonstrated previously that mast cells residing in the FDE lesions play an important role in T cell activation by providing such a nonspecific localized initiating stimulus [8]. Mast cells release preformed cytokines such as tumor necrosis factor α, providing a localized initiating stimulus, and subsequently these cytokines lead to activation of the epidermal T cells through upregulation of cell adhesion molecules on lesional keratinocytes [10].…”

“…2). Because such an abundance of CD8+ T cells in the lesional epidermis is typically observed in FDE [8], we suspected that the eruption was caused by theophylline. Avoidance of theophylline was recommended, but the patient’s parents did not want to avoid this medication because of its clinical efficacy.…”

Trauma-Localized Fixed Drug Eruption: Involvement of Burn Scars, Insect Bites and Venipuncture Sites

“…In this regard, we previously demonstrated that mast cells can provide the locally high cytokine concentrations required to activate intraepidermal CD8+ T cells to exert their cytolytic functions [1, 2]. Indeed, the relatively rapid onset of the FDE lesion after challenge can be well explained by the unique property of mast cells to release preformed cytokines such as TNF-α.…”

“…We have previously demonstrated that abundance of CD8+ intraepidermal T cells in the lesional skin provides a mechanism for the preferential occurrence of FDE lesions at certain skin sites [1, 2, 3]. However, we do not yet know why a particular site out of all parts of the skin was chosen as the initial presentation of FDE lesions: little is known about what causes FDE lesions to appear in their particular areas of predilection.…”