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Epidermal cell production of thymocyte activating factor (ETAF).

Since epidermal Langerhans cells share many of the surface marker characteristics and functions of cells of the monocyte-macrophage series, we sought to determine whether Langerhans cells, like macrophages, produce Interleukin 1 (IL-1), formerly called lymphocyte activating factor. Heterogenous suspensions of murine epidermal cells were cultured for 3days with or without various stimulants and their cell-free supernatants were tested for IL-1 activity in a thymocyte proliferation assay. Significant augmentation of lectin induced thymocyte proliferation was produced by the supernatants of these cultures. However, when epidermal cells were depleted of Langerhans cells by treating with anti-Ia anti-serum and complement, the supernatants still produced significant augmentation. As the augmenting activity was due to a factor found in the supernatants of epidermal cell suspensions devoid of Langerhans cells the factor is called Epidermal Cell Thymocyte Activating Factor (ETAF). ETAF was produced by unstimulated epidermal cells, but significantly more was produced by epidermal cells that were incubated with phorbol myristic acetate, a low molecular weight tumor promoting agent or muramyl dipeptide, the synthetic analog of the cell wall of mycobacterium smegmatis. ETAF production was reduced by X-irradiation and was completely abolished when protein synthesis was inhibited. The molecular weight of this factor was approximately 15,000 dalton, which is similar to the molecular weight of macrophage derived IL-1; its heat stability and pH stability were similar to that of IL-1. ETAF, like IL-1 also enhanced lymphocyte production of Interleukin 2 (IL-2). The data indicate that epidermal cells, devoid of Langerhans cells, are capable of producing factors with IL-1 like activity and may thereby modulate immune responses locally in the skin and perhaps systemically.