THYMIC ENVIRONMENT AND T CELL DIFFERENTIATION

这项工作将采用单克隆抗体特异性不同 胸腺上皮（TE）细胞群体追求两个核心目标， 我们对胸腺在T细胞分化中的作用的理解：1） 表征构成皮质和髓质区域的基质细胞 并确定每个区域特有的抗原， 参与胸腺细胞-上皮细胞相互作用;和2）检查 皮质髓质TE特异性单克隆抗体的作用 细胞对胸腺器官培养物支持胸腺功能的影响 淋巴细胞生成和体外免疫活性T细胞的产生。 一 已经产生了一组单克隆抗体，其表现出至少 当应用于胸腺的冷冻切片时， 光镜水平：整个皮质的所有基质细胞， 髓质;髓质基质细胞;皮质基质细胞;间充质细胞 结缔组织和血管结构。 超微结构 用这些抗体对胸腺进行免疫组织化学研究， 提供上皮区室化的详细表征， 胸腺内的异质性。 这些研究将得到补充， 对这些抗体识别的分子进行生化分析， 从而提供了对皮质抗原的抗原特征的描述， 胸腺的髓质环境。 最后，这些抗体将 检测其影响胎儿胸腺器官功能的能力 体外培养。 待检查的胸腺功能参数将 包括淋巴细胞生成的程度和胸腺细胞的出现 具有不同Lyt-2和L3 T4表型的群体。 此外该 抗体处理的胸腺器官培养物产生 将检查具有免疫活性的胸腺细胞，类似于外周T细胞 通过一系列功能性检测。 这些研究将有助于 对我们理解T细胞分化和定位 TE细胞的不同群体在这个复杂过程中的作用。 本研究中获得的信息也可能被证明是有价值的， 了解胸腺的发育缺陷和胸腺发育的过程 内卷，后者伴随着年龄相关的损失， 人体胸腺功能

The work will employ monoclonal antibodies specific for different populations of thymic epithelial (TE) cells to pursue two aims central to our understanding the thymic role in T cell differentiation: 1) Characterize the stromal cells comprising the cortical and medullary areas of the thymus and identify antigens unique to each area which may be involved in thymocyte-epithelial cell interactions; and 2) Examine the effects of monoclonal antibodies specific for either cortical medullary TE cells on the ability of thymus organ cultures to support thymic lymphopoiesis and the generation of immuncompetent T cells in vitro. A panel of monoclonal antibodies has been generated which exhibit at least four basic labelling patterns when applied to frozen sections of thymus at the light microscopic level: all stromal cells throughout the cortex and medulla; medullary stromal cells; cortical stroma cells; and mesenchymal elements (connective tissue and vascular structures). Ultrastructural immunohistochemical studies of the thymus with these antibodies will provide a detailed characterization of epithelial compartmentalization and heterogeneity within the thymus. These studies will be complemented with biochemical analyses of the molecules recognized by these antibodies, thereby providing a description of the antigenic features of cortical and medullary environments of the thymus. Finally these antibodies will be tested for their ability to affect the function of fetal thymus organ cultures in vitro. Parameters of thymus function to be examined will include the extent of lymphopoiesis and the appearance of thymocyte populations bearing distinct Lyt-2 and L3T4 phenotypes. In addition, the ability of antibody-treated thymus organ cultures to generate immunocompetent thymocytes, resembling peripheral T cells, will be examined by a number of functional assays. These studies will contribute significantly to our understanding of T cell differentiation and address the role of different populations of TE cells in this complex process. Information obtained in this study may also prove to be valuable in understanding developmental defects of the thymus and the process of thymus involution, where the latter is accompanied by an age-related loss of thymus function in man.