TUMOR-NECROSIS-FACTOR-ALPHA IS REQUIRED FOR ACCUMULATION OF DENDRITIC CELLS IN DRAINING LYMPH-NODES AND FOR OPTIMAL CONTACT SENSITIZATION

Following skin sensitization epidermal Langerhans' cells (LC), many of which bear antigen, are stimulated to migrate from the skin and traffic via afferent lymphatics to lymph nodes draining the site of exposure. It has been proposed previously that tumour necrosis factor-alpha (TNF-alpha), a keratinocyte-derived epidermal cytokine (the expression of which is augmented following cutaneous sensitization), provides one signal for LC migration. In the experiments described here the influence of systemically administered neutralizing anti-TNF-alpha antibody on dendritic cell (DC) accumulation in draining lymph nodes has been investigated. Treatment with anti-TNF-alpha inhibited markedly the frequency of DC in draining nodes measured 18 hr following exposure to the skin allergens oxazolone and fluorescein isothiocyanate or to the non-sensitizing skin irritant sodium lauryl sulphate. Similar treatment with anti-TNF-alpha 2 hr prior to primary exposure to oxazolone impaired significantly the efficiency of skin sensitization measured 5 days later as a function of challenge-induced increases in ear thickness. The same antibody administered 18 hr following initial exposure to oxazolone was without effect on skin sensitization. These data confirm the importance of TNF-alpha for the migration of LC from the skin to draining lymph nodes and demonstrate that this cytokine is required for optimal contact sensitization.