USE OF T-CELL HYBRIDOMAS TO STUDY CUTANEOUS IMMUNOLOGY

使用 T 细胞杂交瘤研究皮肤免疫学

• 批准号: 3457208
• 负责人: MICHAEL E BIGBY
• 金额: $ 14.53万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-07 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3457208
• 关键词: T cell receptor; T lymphocyte; antigen presenting cell; cellular immunity; fluoresceins; genetic strain; haptens; hybridomas; immune response genes; immunoconjugates; immunoregulation; isothiocyanates; laboratory mouse; lymphokines; phorbols; radiation immunosuppression; skin hypersensitivity; ultraviolet radiation

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.

这项研究的目的是利用半抗原特异性T细胞 杂交瘤来研究接触的发展和调节 小鼠超敏反应 这些目标将通过以下方式实现： 调查1。对局部应用的半抗原的免疫应答和2. 紫外线B照射和佛波酯对细胞凋亡的影响 皮肤的免疫功能。 我们已经制造出了对荧光素有特异性的T细胞杂交瘤 异硫氰酸酯或三硝基苯酚偶联的抗原呈递细胞（APC）。 这些杂交瘤将用于研究： 名词的身份 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系统中的应用 对局部施用的半抗原的响应;和c. 半抗原特性 在表皮、真皮和其他区域淋巴中出现的APC 致敏小鼠的淋巴结。 我们打算在其他国家制造T细胞杂交瘤， 小鼠品系（C57BL/10和C3H.HEJ），这将使我们能够研究 在已知的小鼠品系中发生接触性超敏反应 对接触性过敏原有不同的反应 局部UVB照射。 为了评估UVB和佛波醇肉豆蔻酸酯乙酸酯（PMA）对 皮肤的免疫功能，我们打算使用半抗原特异性 杂交瘤以确定是否：a.用低剂量局部处理小鼠 UVB照射或PMA照射影响外观和功能能力 表皮、真皮和区域淋巴结中的APC; B.的影响 UVB或PMA可以由淋巴因子（例如，γ-干扰素 IF]或肿瘤坏死因子α [TNF α]），或可被 针对淋巴因子的抗体（例如，γ-IF或TNF α）; c. 菌株对低剂量局部UVB治疗的敏感性差异; d. 在体外用低剂量UVB处理的半抗原偶联的APC， 能够刺激半抗原特异性杂交瘤;并且APC功能可以 用淋巴因子恢复（例如，IL-1），如果UVB的能力缺陷 检测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，并可能对我们的免疫系统产生重大影响 免疫介导性疾病的治疗和预防 皮肤