Gluckman J C, Canque B, Rosenzwajg M
Service d'immunologie biologique, unité de biologie et thérapeutique des pathologies immunitaires et Laboratoire d'immunologie cellulaire de l'Ecole pratique des hautes études, hôpital de la Pitié-Salpêtrière, Paris, France.
Transfus Clin Biol. 1998 Feb;5(1):47-55. doi: 10.1016/s1246-7820(98)80110-9.
Dendritic cells (DC) are the most potent antigen-presenting cells. Thus, ex vivo antigen-pulsed DC are a potentially powerful tool to induce in vivo immunity against tumor-associated or viral antigens. Therefore, culture methods to generate high numbers of DC from bone marrow or blood CD34+ hematopoietic progenitor cells have recently been developed. These methods, which use different combinations of growth factor--mainly granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha and interleukin (IL)-4--make the characterization of DC obtained from CD34+ cells of different origins easier and allow to assess whether DC relate to a unique or distinct differentiation pathways. Monocytes and even macrophages can also directly differentiate into DC in the presence of GM-CSF and IL-4. This has to be reconciled with evidence supporting earlier branching off of the macrophage and DC lineages, and raises questions as to the identity of the latter lineage. Apart from DC of myeloid origin, DC may also originate from lymphoid progenitors. Because the capacity of DC to capture, process and present antigens is known to vary according to their differentiation stage, and lymphoid DC might behave differently from lymphoid DC in this respect, the definition of which type of DC to use for immunotherapy must be more precise, in order to avoid detrimental side effects or results. From a practical point of view, it is also necessary to define the most appropriate cytokine combinations and schedules thereof to optimize proliferation and differentiation of DC from different origins. These conditions should then be applied to generated DC for their efficient and safe use for clinical immunotherapy.
树突状细胞(DC)是最有效的抗原呈递细胞。因此,体外抗原脉冲DC是诱导体内针对肿瘤相关或病毒抗原免疫的潜在强大工具。因此,最近已开发出从骨髓或血液CD34 +造血祖细胞中产生大量DC的培养方法。这些方法使用不同组合的生长因子 - 主要是粒细胞/巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子(TNF)-α和白细胞介素(IL)-4 - 使得从不同来源的CD34 +细胞获得的DC的表征更容易,并允许评估DC是否与独特或不同的分化途径相关。在GM-CSF和IL-4存在的情况下,单核细胞甚至巨噬细胞也可以直接分化为DC。这必须与支持巨噬细胞和DC谱系早期分支的证据相协调,并引发了关于后一种谱系身份的问题。除了髓系来源的DC外,DC也可能起源于淋巴祖细胞。由于已知DC捕获、加工和呈递抗原的能力会根据其分化阶段而变化,并且在这方面淋巴样DC的行为可能与髓样DC不同,因此为了避免有害的副作用或结果,用于免疫治疗的DC类型的定义必须更加精确。从实际角度来看,还需要定义最合适的细胞因子组合及其方案,以优化不同来源DC的增殖和分化。然后应将这些条件应用于生成的DC,以便将其高效安全地用于临床免疫治疗。