HUMAN THYMIC/EPITHELIAL T CELL INTERACTION

成熟T淋巴细胞与胸腺微环境的相互作用 对功能成熟的T淋巴细胞的发育至关重要。 异常的T细胞成熟可导致免疫缺陷、自身免疫和 T细胞白血病和淋巴瘤。表皮已经被牵连成 另一种组织可能作为成熟T细胞的诱导环境 淋巴细胞及其与胸腺上皮的许多相似之处 细胞已经被记录在案。这项提议的总体目标是 评估表皮与T淋巴细胞的相互作用。表皮的能力 角质形成细胞(EK)作为T淋巴细胞的辅助细胞，包括 将研究静止的T细胞、激活的T细胞和T细胞克隆。 如果EK作为辅助细胞或抗原提呈细胞，尤其是对 活化的T细胞那么EK在体内可能起重要的放大作用 持续的免疫反应，特别是在慢性炎症性疾病中 回应。EK结合并刺激细胞增殖的能力 T淋巴细胞谱系的未成熟细胞将用T细胞- T细胞增殖的上皮结合实验和标准实验。这个 这些研究的结果应该提供有关能力的信息 在正常人中作为胸腺外T细胞成熟的部位 以及反常的情况。T细胞的成熟状态及相关基因的表达 炎症性皮肤中T细胞中的T细胞受体基因 疾病和皮肤T细胞恶性肿瘤将使用 免疫荧光、原位杂交和Northern印迹技术 识别T细胞受体基因(α、β、伽马)的mRNA转录本。 淋巴细胞对表皮细胞的作用将被研究。这些 研究将包括T细胞对表皮产生IL-1的调节 细胞以及T细胞介导的细胞表面标志物的调节(HLA- DR、ICAM-1)。T细胞来源的IL-2对小鼠外周血中IL-2的影响 将研究表皮细胞的增殖情况。一种细胞毒性抗- 原资助期产生的成纤维细胞和巨噬细胞抗体 将包括对目标的生化鉴定 分子和可能的功能抑制试验。

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.