EPITHELIAL DIFFERENTIATION COMPARISON OF SKIN & THYMUS

皮肤上皮分化比较

• 批准号: 3156957
• 负责人: KAY H SINGER
• 金额: $ 7.55万
• 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/3156957
• 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淋巴细胞与胸腺的相互作用 微环境是功能发展的关键 成熟的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。 这可能是一个成熟的T的诱导环境 淋巴细胞与表皮和胸腺的许多相似之处 上皮细胞已经被记录在案。这样做的总体目标是 建议评估表皮-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 并将对T细胞克隆进行研究。如果EK作为从犯 细胞或抗原提呈细胞，尤其是活化的T细胞 那么EK可能在体内发挥重要的作用，在放大 持续的免疫反应，特别是在慢性 炎症反应。EK与AND结合的能力 刺激T淋巴细胞未成熟细胞的增殖 血统将使用T细胞-上皮结合分析和 T细胞增殖的标准检测。这些研究的结果 研究应该提供有关能力的信息 表皮作为胸腺外T细胞成熟的部位 正常和异常的情况。T细胞的成熟状态 以及T细胞受体基因在T细胞中的表达 皮肤与炎症性皮肤病和皮肤T细胞 恶性肿瘤将使用免疫荧光来确定，在 原位杂交和Northern印迹技术鉴定mRNA T细胞受体基因(α、β、伽马)的转录本。这个 T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IL-1产生的调节 表皮细胞与T细胞介导的细胞调控 表皮细胞表面标志(人类白细胞抗原DR、细胞间黏附分子-1)。这个 T细胞来源的IL-2对表皮细胞增殖的影响 被调查。一种细胞毒性的抗成纤维细胞和巨噬细胞 在原资助期内产生的抗体将 特征包括靶标的生化鉴定 分子和可能的功能分析的抑制。