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[朗格汉斯细胞:从体外培养到用于细胞免疫治疗]

[The Langerhans cell: from in vitro production to use in cellular immunotherapy].

作者信息

Schmitt D

机构信息

Laboratoire de recherche Peau humaine et Immunité, INSERM Unité 346, Dermatologie, Pavillon R, Hôpital Edouard-Herriot, 69437 Lyon.

出版信息

J Soc Biol. 2001;195(1):69-74.

Abstract

Dendritic cells constitute a family of antigen presenting cells defined by their morphology and their capacity to initiate primary immune response. Langerhans cells are paradigmatic dendritic cells, described in 1868 by a young medical student, Paul Langerhans in Berlin. Langerhans cells are present with epithelial cells in the epidermis, bronchi and mucosae. After antigenic challenge, Langerhans cells migrate into the T cell areas of proximal lymph nodes where they act as professional antigen-presenting cells. Langerhans cells originate in the bone marrow and CD34+ hematopoïetic progenitors are present in cord blood or circulating blood. They are actively involved in skin lesions of allergic contact dermatitis or atopic dermatitis, in cancer immunosurveillance and are infected by HIV in AIDS. Since 1992, Langerhans cells may be generated in vitro from CD34+ cord blood or circulating blood progenitors by culture with GM-CSF and TNF alpha, as well as from peripheral blood monocytes by culture with GM-CSF, IL4 and TGF beta 1. The possibility to obtain from the blood, the circulating progenitors of dendritic cells and the subsequent possibility to harvest a large number of these cells through in vitro culture using growth factors, have given rise to several very interesting therapeutic perspectives, especially in the field of anti-cancer immunotherapy. In dermatology advanced studies have concerned malignant melanomas. Anti-melanoma immunization trials were performed in patients, through dendritic cells charged with melanoma antigens. Side effects appear to be limited. Injections of antigenically charged dendritic cells were performed subcutaneously, intravenously or in the lymph nodes. Positive clinical responses were obtained with, in some cases, complete remission of the metastasis. These results open a particularly interesting perspective in the field of cancer treatment.

摘要

树突状细胞是一类抗原呈递细胞,其定义基于它们的形态以及启动初次免疫反应的能力。朗格汉斯细胞是典型的树突状细胞,1868年由柏林的一名年轻医学生保罗·朗格汉斯首次描述。朗格汉斯细胞与表皮、支气管和黏膜中的上皮细胞共存。受到抗原刺激后,朗格汉斯细胞迁移至近端淋巴结的T细胞区域,在那里它们作为专职抗原呈递细胞发挥作用。朗格汉斯细胞起源于骨髓,脐带血或循环血液中存在CD34+造血祖细胞。它们积极参与过敏性接触性皮炎或特应性皮炎的皮肤病变、癌症免疫监视,并在艾滋病中被HIV感染。自1992年以来,通过与GM-CSF和TNFα一起培养,可从CD34+脐带血或循环血液祖细胞体外生成朗格汉斯细胞,也可通过与GM-CSF、IL4和TGFβ1一起培养从外周血单核细胞生成。从血液中获取树突状细胞的循环祖细胞,并随后通过使用生长因子进行体外培养收获大量此类细胞的可能性,引发了一些非常有趣的治疗前景,尤其是在抗癌免疫治疗领域。在皮肤病学方面,深入研究涉及恶性黑色素瘤。通过负载黑色素瘤抗原的树突状细胞对患者进行抗黑色素瘤免疫试验。副作用似乎有限。负载抗原的树突状细胞通过皮下、静脉内或淋巴结注射。在某些情况下,获得了阳性临床反应,转移灶完全缓解。这些结果为癌症治疗领域开辟了一个特别有趣的前景。

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