The immunological basis of lichenoid tissue reaction.

An autoimmune attack by T cells on the epidermis is the primary pathological event in the lichenoid tissue reaction (LTR). The severity of epidermal damage in the LTR is dependent on the relative balance between the intensity and perpetuation of T cell activation and the capacity of epidermal cells to protect from the attack. In natural disease processes, T cells activated by some exogenous agents migrate from the blood to the skin sites and invade the epidermis. Although this epidermotropic migration of T cells resulting in epidermal destruction is a complicated multistep process, this can be bypassed in fixed drug eruption (FDE). Thus, FDE is the most simplified disease model for investigating the pathogenesis of the LTR, in that large numbers of effector CD8+ T cells persist as a stable population in the resting lesions without causing epidermal damage and activation of these T cells resulting in localized epidermal injury can only be induced after administration of the causative drugs. Based on the findings observed with these CD8+ skin-resident T cells, we hypothesize that CD8+ T cells primed during viral infections could evolve into long-lived effector memory phenotype T cells; they would be subsequently trapped either specifically or nonspecifically in the inflamed skin sites and eventually persist as a stable population. Once cross-reacted with exogenous stimuli, such as drug or self-antigens, however, they would become effectors of epidermal damage as seen in various lichenoid skin diseases.