BIOLOGY OF THE THY-1 ANTIGEN BEARING EPIDERMAL CELLS

University Of Texas Sw Med Ctr/Dallas, Dallas TX

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Abstract

DESCRIPTION: (Adapted from the applicant's abstract) - DETC have been characterized phenotypically by the expression of T cell receptors and functionally by in vivo immunosuppressive activities. The principal investigator has observed that DETC secrete biologically relevant amounts of IL-13 which inhibits the production of proinflammatory cytokines by both keratinocytes and Langerhans cell lines. Very little information is available regarding the function of IL-13 in skin, and the principal investigator proposes to study the biology of this cytokine. Their hypothesis is that IL-13 production by DETC silences immunologic response of neighboring keratinocytes and LC to proinflammatory stimuli, suppressing subsequent immune reactions. They suggest that there is a costimulatory role for LC in supporting IL-13 secretion. They have cloned two glycoproteins called dectin-1 and -2 that are expressed by LCs, and recombinant dectin-1 binds to the surface of DETC. Also Langerhans cell-dependent IL-13 secretion is blocked by anti-dectin-2 monoclonal antibodies. There are five specific aims. 1) They wish to identify in vitro effects of IL-13 on immunologic properties of keratinocytes and LCs. Epidermal cells will be cultured in the presence of IL-13 and examined for changes in cytokine production, surface phenotype, mitotic potential, and antigen presentation. 2) They wish to determine the in vivo impact of IL-13 when overproduced locally. They will target IL-13 gene expression in DETC in mouse skin by delivery by a gene gun of a IL-13 cDNA under control of the TCR -chain promoter. 3) They will test the extent to which IL-13 accounts for immunosuppressive activities, by sensitization of mice through skin sites where recombinant IL-13 is injected locally or overproduced by DETC. 4) They wish to characterize the dectin ligands expressed on DETC by mammalian cell expression cloning using his-dectin-1 as a probe. 5) They wish to study mechanisms that may regulate IL-13 production in DETC by examining environmental stimuli as opposed to internal stimuli. Through these five specific aims they intend to uncover unique activities of IL-13 in the skin.