EPITHELIAL DIFFERENTIATION: COMPARISON OF SKIN & THYMUS

上皮分化：皮肤比较

• 批准号: 3156952
• 负责人: KAY H SINGER
• 金额: $ 8.19万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156952
• 关键词: T lymphocyte; autoimmune disorder; cell cell interaction; cell differentiation; cell population study; epidermal growth factor; epithelium; gene expression; histocompatibility antigens; human tissue; immunofluorescence technique; inflammation; keratinization; keratinocyte; laboratory mouse; leukocyte activation /transformation; lymphocytic leukemia; lymphoma; messenger RNA; mixed tissue /cell culture; physical chemical interaction; retinoids; skin; thymus

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 T 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 functional assays.

成熟T淋巴细胞与胸腺细胞的相互作用 微环境对于功能性的发展至关重要 成熟T淋巴细胞 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， 淋巴瘤 表皮被认为是另一种组织 这可能作为一个诱导环境， 淋巴细胞和表皮和胸腺之间的许多相似之处 上皮细胞已经被记录。 这件事的总目标是 建议是评估表皮- T淋巴细胞相互作用。 表皮角质形成细胞（EK）作为辅助细胞的能力 T淋巴细胞，包括静息T细胞、活化T细胞 并研究T细胞克隆。 如果EK作为从犯 细胞或抗原呈递细胞，特别是活化的T细胞 那么EK在体内可能在放大 持续的免疫反应，特别是在慢性 炎症反应。 EK结合和 刺激T淋巴细胞的未成熟细胞增殖 将使用T细胞-上皮细胞结合测定来检查谱系， T细胞增殖的标准测定。 的结果予以 研究应提供有关能力的信息， 表皮作为胸腺外T细胞成熟的场所， 正常和异常的情况。 T细胞成熟的状态 以及T细胞受体基因在T细胞中的表达， 炎症性皮肤病皮肤与皮肤T细胞 恶性肿瘤将使用免疫荧光测定， 原位杂交和北方印迹技术鉴定mRNA T细胞受体基因（α，β，γ）的转录物。 的 将研究T淋巴细胞对表皮细胞的作用。 这些研究将包括T细胞调节IL 1的产生， 表皮细胞以及T细胞介导的细胞调节 表皮细胞表面标志物（HLA-DR、ICAM-1）。 的 T细胞来源的IL-2对表皮细胞增殖的影响将 追究 一种细胞毒性抗成纤维细胞和巨噬细胞 在最初的资助期内产生的抗体将 其特征包括靶标的生化鉴定 分子和功能测定的可能抑制。