HUMAN THYMIC/EPITHELIAL T CELL INTERACTION

成熟T淋巴细胞与胸腺微环境的相互作用 对于功能成熟的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、自身免疫和免疫缺陷。 T细胞白血病和淋巴瘤。 表皮被认为是 另一种组织可能作为T细胞成熟的诱导环境， 淋巴细胞以及表皮和胸腺上皮之间的许多相似性 细胞被记录下来。 本提案的总体目标是 评估表皮-T淋巴细胞相互作用。 表皮的能力 角质形成细胞（EK）作为辅助细胞的T淋巴细胞，包括 将研究静息T细胞、活化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，特别是 激活的T细胞，那么EK可能在体内放大 持续的免疫反应，特别是在慢性炎症 应答 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使用T细胞- 上皮结合测定和T细胞增殖的标准测定。 的 这些研究的结果应提供有关能力的信息， 作为胸腺外T细胞成熟的部位， 和异常情况。 T细胞的成熟状态和 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、原位杂交和北方印迹技术， 鉴定来自T细胞受体基因（α、β、γ）的mRNA转录物。 将研究淋巴细胞对表皮细胞的影响。 这些 研究将包括T细胞调节IL 1的产生， 细胞以及T细胞介导的细胞表面标志物（HLA-1）调节 DR、ICAM-1）表达。 T细胞源性IL-2对人外周血淋巴细胞增殖的影响 将研究表皮细胞增殖。 一种细胞毒性抗- 原资助期内产生的成纤维细胞和巨噬细胞抗体 将进行表征，包括靶标的生化鉴定 分子和可能的功能抑制测定。

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.