MODULATION OF EPIDERMAL LANGERHANS CELL FREQUENCY BY TUMOR-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 Langerh ans' cells (LC) which are induced to migrate from the skin, via the af ferent lymphatics, to lymph nodes. We demonstrated previously that int radermal exposure of mice to homologous; but not human, recombinant tu mour 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 migra tion. In the present study we have examined the influence of dermal TN F-alpha on the frequency of LC within the epidermis. Intradermal injec tion 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 D C. The density of LC was unaffected by the same amount of human TNF-al pha of comparable specific activity or by murine granulocyte-macrophag e colony-stimulating factor (GM-CSF). These data provide additional ev idence that TNF-alpha provides an important signal for the migration o f LC from the epidermis.