EPITHELIAL DIFFERENTIATION COMPARISON OF SKIN & THYMUS

皮肤上皮分化比较

• 批准号: 3156958
• 负责人: KAY H SINGER
• 金额: $ 7.09万
• 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/3156958
• 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 淋巴细胞与胸腺之间的相互作用 微环境对功能发育至关重要 成熟的T淋巴细胞。 T 细胞成熟异常可能导致 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 T 成熟的诱导环境 淋巴细胞以及表皮和胸腺之间的许多相似之处 上皮细胞已被记录。 本次活动的总体目标 建议是评估表皮-T 淋巴细胞的相互作用。 表皮角质形成细胞 (EK) 作为辅助细胞的能力 T淋巴细胞的细胞，包括静息T细胞、活化T细胞 T细胞克隆将被研究。 如果EK作为附件 细胞或抗原呈递细胞，特别是活化的T细胞 那么 EK 可能在体内发挥重要作用 持续的免疫反应，特别是慢性免疫反应 炎症反应。 EK 结合 和 的能力 刺激T淋巴细胞未成熟细胞增殖 将使用 T 细胞-上皮结合测定来检查谱系 T 细胞增殖的标准测定。 这些结果 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 正常和异常情况。 T细胞成熟状态 以及T细胞受体基因在T细胞中的表达，这些T细胞归巢于 炎症性皮肤病中的皮肤和皮肤 T 细胞 恶性肿瘤将使用免疫荧光来确定， 原位杂交和 Northern blot 技术鉴定 mRNA T 细胞受体基因（α、β、γ）的转录本。 这 将研究T淋巴细胞对表皮细胞的影响。 这些研究将包括 T 细胞对 IL 1 产生的调节 表皮细胞以及 T 细胞介导的细胞调节 表皮细胞上的表面标记（HLA-DR、ICAM-1）。 这 T 细胞衍生的 IL 2 对表皮细胞增殖的影响 被调查。 细胞毒性抗成纤维细胞和巨噬细胞 原资助期内产生的抗体将 特征包括目标的生化鉴定 分子和功能测定的可能抑制。