HUMAN THYMIC/EPITHELIAL T CELL INTERACTION

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Interactions between maturing T lymphocytes and the thymic microenvironment are critical for the development of functionally mature T lymphocytes. Aberrant T cell maturation can result in immunodeficiency, autoimmunity and T cell leukemias and lymphomas. The epidermis has been implicated as another tissue that might serve as an inductive environment for maturing T lymphocytes and many similarities between epidermis and thymic epithelial cells have been documented. The general goal of this proposal is to evaluate epidermal -T lymphocyte interactions. The ability of epidermal keratinocytes (EK) to serve as accessory cells for T lymphocytes including resting T cells, activated T cells and T cell clones will be investigated. If EK serve as accessory cells or antigen presenting cells, particularly to activated T cells then EK may play a significant role in vivo in amplifying an ongoing immune response and particularly in chronic inflammatory responses. The ability of EK to bind to and stimulate proliferation of immature cells of the T lymphocyte lineage will be examined using T cell- epithelial binding assays and standard assays of T cell proliferation. The results of these studies should provide information regarding the ability of epidermis to serve as a site of extrathymic T cell maturation in normal and aberrant situations. The state of T cell maturation and expression of T cell receptor genes in T cells that home to the skin in inflammatory skin disease and cutaneous T cell malignancies will be determined using immunofluorescence, in situ hybridization and Northern blot techniques to identify mRNA transcripts from T cell receptor genes (alpha, beta, gamma). The effects of lymphocytes on epidermal cells will be investigated. These studies will include T cell regulation of Il 1 production by epidermal cells as well as T cell-mediated regulation of cell surface markers (HLA- DR, ICAM-1) on epidermal cells. The effects of T cell derived IL 2 on epidermal cell proliferation will be investigated. A cytotoxic anti- fibroblast and macrophage antibody produced in the original funding period will be characterized including biochemical identification of target molecules and possible inhibition of function assays.