USE OF T-CELL HYBRIDOMAS TO STUDY CUTANEOUS IMMUNOLOGY

该方案中的研究旨在利用半抗原特异性T细胞 用杂交瘤研究接触的发育和调节 小鼠的过敏反应。这些目标将通过以下方式实现 研究1.局部应用半抗原的免疫反应和2. 中波紫外线照射和佛波酯对小鼠心肌细胞生长的影响 皮肤的免疫功能。 我们已经研制出针对荧光素的T细胞杂交瘤 异硫氰酸酯或三硝基苯酚偶联抗原提呈细胞(APC)。 这些杂交瘤将被用来研究：a.名词性 抗原(半抗原加蛋白质)，负责诱导 接触性超敏反应；b.T细胞受体基因在免疫中的应用 局部应用半抗原的反应；以及C.半抗原的特性 带有出现在表皮、真皮和其他区域淋巴中的APC 致敏小鼠的结节。我们打算在其他地方制造T细胞杂交瘤 小鼠品系(C57BL/10和C3H.HEJ)，将使我们能够研究 已知的小鼠品系的接触性超敏反应 对接触变应原有不同的反应性和不同的反应 至局部UVB照射。 目的：探讨中波紫外线(UVB)和佛波酯(PMA)对小鼠心脏功能的影响。 皮肤的免疫功能，我们打算用半抗原特异性 杂交瘤以确定是否：A.用小剂量局部治疗小鼠 UVB照射或联合PMA对外观和功能的影响 表皮、真皮和区域淋巴结内的APC；B.影响 UVB或PMA可由淋巴因子(如干扰素 If]或肿瘤坏死因子α[TNFpha])或可被阻断 针对淋巴因子的抗体(如Gamma-IF或TNFpha)；c. 菌株对低剂量、局部UVB治疗的敏感性差异； 体外小剂量UVB处理的半抗原偶联型APC 能够刺激半抗原特异性杂交瘤；APC功能可以 淋巴因子修复(例如，IL-1)如果UVB能力存在缺陷 检测到刺激杂交瘤的经处理的APC。这些 研究将扩大我们对皮肤作为一种 免疫系统的组成部分，并可能对我们的 关于免疫介导性疾病治疗和预防的几点思考 皮肤。

The research in this proposal is designed to utilize hapten specific T-cell hybridomas to investigate the development and regulation of contact hypersensitivity in mice. These objectives will be achieved by investigating 1. the immune response to topically applied haptens and 2. the effects of ultraviolet B irradiation and phorbol esters on the immunologic functions of the skin. We have made T-cell hybridomas that are specific for fluorescein isothiocyanate or trinitrophenol coupled antigen presenting cells (APCs). These hybridomas will be used to study: a. the identify of the nominal antigens(hapten plus protein) that are responsible for the induction of contact hypersensitivity; b. T-cell receptor gene usage in the immune response to topically applied haptens; and c. characteristics of hapten bearing APCs that appear in the epidermis, dermis, and other regional lymph nodes of sensitized mice. We intend to make T-cell hybridomas in other strains of mice (C57BL/10 and C3H.HEJ) that will allow us to study the development of contact hypersensitivity in strains of mice that are known to have different reactivity to contact allergens and different responses to local UVB irradiation. To assess the effects of UVB and phorbol myristate acetate (PMA) on the immunologic functions of the skin, we intend to use hapten specific hybridomas to determine whether: a. treatment of mice locally with low dose UVB irradiation or with PMA affects the appearance and functional capacity of APCs in the epidermis, dermis and regional lymph nodes; b. the effects of UVB or PMA can be produced by lymphokines (eg. gamma-interferon [gamma- IF] or tumor necrosis factor alpha [TNFalpha]) or can be blocked by antibodies directed against lymphokines (eg. gamma-IF or TNFalpha); c. strain differences in sensitivity to low dose, local UVB treatment; d. hapten coupled APCs which are treated with low dose UVB in vitro are capable of stimulating hapten-specific hybridomas; and APC function can be restored with lymphokines (eg. IL-1) if defects in the ability of UVB treated APCs to stimulate the hybridomas are detected. These investigations will broaden our understanding of the role of the skin as a component of the immune system and may have a significant impact on our ideas about the therapy and prevention of immune mediated diseases of the skin.