Control of Langerhans' cell density by a skin tumour-derived cytokine.

Langerhans' cells (LC) are bone marrow-derived dendritic antigen-presenting cells (APC) found in the epidermis of mammals. It is not known why they accumulate in the epidermis. Human and murine skin tumours are infiltrated with large numbers of LC, however previous experiments have shown that this does not seem to be associated with immune responses against the tumours. Here we show that a squamous-derived tumour cell line (T7) produces a cytokine which increases the number of LC in normal epidermis. T7 supernatant increased the density of LC in both mice syngeneic to the T7 cells (Skh:HR-1) as well as in BALB/c mice, indicating that the cytokine is not genetically restricted. The cytokine is a protein, not a prostaglandin, with a MW of > 12,000 as its production was inhibited by cycloheximide but not indomethacin and it could not be removed by dialysis against a 12,000 MW cut-off membrane. The increased numbers of LC found in tumour supernatant-treated epidermis expressed Ia as well as the molecule defined by the J11d monoclonal antibody, which is expressed by LC but not macrophages, confirming that these cells are LC. Another squamous-derived skin tumour, T79, which is not infiltrated with large numbers of LC when inoculated into syngeneic mice, did not produce a factor capable of increasing the density of LC. Hence these studies demonstrate either the activity of a novel cytokine or a new biological activity of a previously described cytokine. It is most likely that this cytokine increased the number of LC by attracting precursors into the epidermis. As the cytokine was produced by transformed squamous cells it is also possible that this cytokine is responsible for attracting LC into normal epidermis.