Interleukin-16 supports the migration of Langerhans cells, partly in a CDL4-independent way

Migration of cutaneous dendritic cells is essential for the induction of pr imary immune responses. Chemotaxis plays an important part in guiding migra ting cells through the skin. Therefore, we investigated the influence of in terleukin-16, a potent chemoattractant, on the migratory properties of cuta neous dendritic cells. Interleukin-16 added to murine and human skin explan t cultures, enhanced emigration of Langerhans cells as well as dermal dendr itic cells out of the skin. In contrast to tumor necrosis factor-a, intrade rmally injected interleukin-16 did not reduce the density of Langerhans cel ls suggesting a chemotactic rather than a mechanistic migration-inducing ef fect of interleukin-16, In support of these findings, the known migration-p romoting effect of tumor necrosis factor-a in skin explant cultures could b e neutralized by anti-interleukin-16 antibody and vice versa, indicating di fferent but cooperative ways of action for both cytokines. In whole skin ex plant cultures blocking of the interleukin-16 effect was also achieved with a monoclonal antibody against CD4, the receptor for interleukin-16, In con trast, in cultures of murine epidermis alone no blocking by anti-CD4 became obvious and in CD4-deficient mice Langerhans cell migration in response to interleukin-16 was maintained. This suggests that another receptor for int erleukin-16 might be operative for Langerhans cells in the mouse epidermis, Finally, we detected interleukin-16-positive cells in the dermis of skin e xplants, tumor necrosis factor-a-treated and contact allergen-treated skin. Taken together, it seems likely that locally secreted interleukin-16 might serve to enhance the migration of cutaneous dendritic cells and optimize t he response to foreign antigen encountering the skin.