Communication between cells of the immune system mediated by polypeptides known as cytokines. Keratinocytes, the predominant cellular element of epidermal epithelium, produce factors now known to be identical to cytokines produced by immune cells (Interleukin 1 (IL-1), Interleukin 3 (IL-3), and granulocyte macrophage colony stimulating factor (GM-CSF)). Very recently, it was shown that one of these keratinocyte cytokines (GM-CSF) is a T cell growth factor, and it now appears that """"""""keratinocyte derived T cell growth factor"""""""" (KTGF) and GM-CSF are identical. The effects of IL-1 on T cell activation and of IL-3 on T cell differentiation are well established; therefore, all three cytokines have important effects on T lymphocytes. The idea that cells not normally considered part of the immune system can influence the behavior of immune cells by producing immunologically active cytokines is novel. While certain keratinocyte cytokines may influence mature T cells in the microenvironment of the skin, others can induce the maturation of T cell precursors. This latter activity may to some extent be analogous to the maturation of T cells in the thymus. A variety of diseases, including cutaneous T cell lymphoma (the most common adult lymphoma), are characterized by infiltration of the skin with normal, activated, or malignant T cells. The identification of three potent epidermal epithelial cytokines capable of exerting specific effects of T cells suggests that the pathogenesis of these diseases may be the dysfunctional release of, or response to, these cytokines. In turn, it is proposed that T cells and their products regulate keratinocyte cytokine production, thus creating a feedback loop between the immune system and epidermal epithelium. In this proposal, recombinant cytokines and cDNA probes homologous to cytokine mRNA will be used to investigate 1) the effect of keratinocyte cytokines on T cells under defined circumstances, 2) the effect of T cell cytokines on keratinocyte cytokine production, 3) whether human keratinocytes, like murine keratinocytes, produce GM-CSF, 4) whether thymic epithelial cells produce cytokines identical to keratinocyte cytokines, and 5) whether keratinocytes and/or their cytokines induce the same effects on T cell differentiation as do thymic epithelial cells.
