THYMIC ENVIRONMENT AND T CELL DIFFERENTIATION

在胸腺环境的影响下，胸腺环境由骨骼组成 T细胞的几个重要方面--骨髓来源细胞和上皮 分化发生，包括抗原受体的表达， 建立MHC限制性抗原识别和自我耐受。 了解胸腺上皮(TE)对T细胞的贡献 差异化一直受到缺乏关于 胸腺上皮。拟议的工作将产生TE细胞系和 利用这些细胞系对TE进行生化和 在功能上。代表皮质和髓质TE Will的细胞系 检查他们与胸腺细胞的物理联系能力 体外亚群，分泌影响胸腺细胞的细胞因子 增殖/分化，并在细胞内提呈抗原 主要组织相容性复合体分子的背景。这些细胞系 将被用来产生一组针对 由皮质和髓质TE群体表达的细胞表面分子。 将使用抗TE抗体对细胞进行免疫化学表征 不同群体胸腺上皮细胞表面分子的表达 细胞，并鉴定皮质和髓质胸腺特有的分子 上皮细胞。这些分子的免疫化学研究将是 辅以免疫电子显微镜研究，以准确地定义 它们在胸腺内的原位分布。最后，通过测试 这些抗上皮细胞抗体对胸腺功能的影响 在体外，这些上皮细胞表面分子参与了 将评估T细胞分化的过程。这些研究 将利用多参数流式细胞术分析胸腺细胞 在抗TE单抗存在下的种群分化 皮质或髓质TE的特异性抗体。这一事件的意义 拟议的工作是，它将从以下方面定义胸腺环境 共同构成的上皮细胞表面和/或细胞因子 胸腺环境。对组成成分的表征 胸腺环境将导致对这一过程的更清晰的理解 T细胞分化，并可能导致治疗的设计 增强胸腺功能的方法。

Under the influence of the thymic environment, which is comprised of bone marrow derived cells and epithelium, several important aspects of T cell differentiation occur, including antigen receptor expression, establishment of MHC-restricted antigen recognition, and self-tolerance. Understanding the contributions of thymic epithelium (TE) to T cell differentiation has been hampered by a lack of information regarding thymic epithelium. The proposed work will generate TE cell lines and use these cell lines to characterize TE biochemically and functionally. Cell lines representative of cortical and medullary TE will be examined for their ability to physically associate with thymocyte subpopulations in vitro, to secrete cytokines affecting thymocyte proliferation/ differentiation, and to present antigen in the context of major histocompatibility complex molecules.These cell lines will be used to generate a panel of monoclonal antibodies specific for cell surface molecules expressed by cortical and medullary TE populations. Anti-TE antibodies will be used to immunochemically characterize the cell surface molecules expressed by different populations of thymic epithelium cells and to identify molecules unique to cortical and medullary thymic epithelial cells. Immunochemical studies of these molecules will be complemented by immunoelectron microscopic studies to precisely define their in situ distribution within the thymus. Finally, by testing the effects of these anti-epithelial antibodies on thymic function in vivo and vitro, the participation of these epithelial cell surface molecules in the process of T cell differentiation will be assessed. These studies will utilize multi-parameter flow cytometry to analyze thymocyte populations differentiating in the presence of anti-TE monoclonal antibodies specific for cortical or medullary TE. The significance of the proposed work is that it will define the thymic environment in terms of the epithelial cell surface and/or cytokines that collectively constitute the thymic environment. Characterization of the constituent components of the thymic environment will lead to a clearer understanding of the process of T cell differentiation and may lead to the design of therapeutic approaches to enhance thymic function.