TUMOR-NECROSIS-FACTOR-ALPHA IS REQUIRED FOR ACCUMULATION OF DENDRITICCELLS 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 traff ic via afferent lymphatics to lymph nodes draining the site of exposur e. 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 influe nce of systemically administered neutralizing anti-TNF-alpha antibody on dendritic cell (DC) accumulation in draining lymph nodes has been i nvestigated. Treatment with anti-TNF-alpha inhibited markedly the freq uency 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 w ith anti-TNF-alpha 2 hr prior to primary exposure to oxazolone impaire d significantly the efficiency of skin sensitization measured 5 days l ater as a function of challenge-induced increases in ear thickness. Th e same antibody administered 18 hr following initial exposure to oxazo lone was without effect on skin sensitization. These data confirm the importance of TNF-alpha for the migration of LC from the skin to drain ing lymph nodes and demonstrate that this cytokine is required for opt imal contact sensitization.