Induction by tumour necrosis factor α of dose-related changes in Langerhans cell frequency in mice

Abstract It has been demonstrated previously that tumour necrosis factor α (TNF-α) provides an important signal for the migration of epidermal Langerhans cells (LC) from the skin. Intradermal administration to mice of homologous recombinant TNF-α induces both a rapid reduction in the frequency of LC local to the site of exposure and, somewhat later, an accumulation of dendritic cells in draining lymph nodes. It has been proposed recently, however, that the influence of TNF-α on LC function may be dose-dependent in nature with lower concentrations inducing migration, but higher concentrations immobilizing LC in the epidermis. To investigate this proposal we examined the kinetics and dose-response relationships of TNF-α-induced LC migration in mice. At all concentrations tested (50, 150 or 300 ng/ear), intradermal exposure to TNF-α caused within 30 min a significant reduction in the frequency of MHC class II (Ia)⁺ LC within epidermal sheets. With the lower concentrations of TNF-α this effect was still apparent when LC were enumerated in the epidermis up to 4 h following cytokine treatment. In contrast, however, exposure of mice to 300 ng of TNF-α was consistently associated with a considerably less marked, and statistically insignificant, reduction in LC frequency by 4 h. These data indicate that at all concentrations of the cytokine examined here, TNF-α was able to stimulate a rapid (within 30 min) reduction in epidermal LC numbers, but that the rapidity with which the epidermis was repopulated following the initiation of LC migration was influenced by the concentration of TNF-α administered. It is suggested that TNF-α may influence not only the tempo of LC migration, but also the kinetics of epidermal repopulation.