Modulation of epidermal Langerhans' cell frequency by tumour necrosis factor-alpha

During the induction phase of skin sensitization, dendritic cells (DC), many of which bear high levels of antigen, accumulate in lymph nodes draining the site of exposure. These DC derive from epidermal Langerhans' cells (LC) which are induced to migrate from the skin, via the afferent lymphatics, to lymph nodes. We demonstrated previously that intradermal exposure of mice to homologous, but not human, recombinant tumour necrosis factor-alpha (TNF-alpha) also causes an accumulation of DC in draining nodes, the implication being that the local production of this cytokine by epidermal cells provides one stimulus for LC migration. In the present study we have examined the influence of dermal TNF-alpha on the frequency of LC within the epidermis. Intradermal injection of mice with 25 ng or greater murine recombinant TNF-alpha caused a significant reduction in LC numbers within 30 min of exposure. The same treatment did not influence the frequency of Thy-1+ epidermal DC. The density of LC was unaffected by the same amount of human TNF-alpha of comparable specific activity or by murine granulocyte-macrophage colony-stimulating factor (GM-CSF). These data provide additional evidence that TNF-alpha provides an important signal for the migration of LC from the epidermis.