In vitro generation of human dendritic cells and cell therapy.
In vitro generation of human dendritic cells and cell therapy.
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发表时间：
1997-09
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通讯作者：
Gluckman Jc;B. Canque;F. Chapuis;M. Rosenzwajg
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作者：
Gluckman Jc;B. Canque;F. Chapuis;M. Rosenzwajg
树突状细胞(DC)是最强大的抗原提呈细胞：只有它们才能激发初始T淋巴细胞，甚至诱导产生细胞毒性T淋巴细胞来产生可溶性抗原。因此，体外抗原致敏的DC是一种潜在的强大工具，可以诱导T细胞对病毒或肿瘤相关抗原的反应。由于DC本身的稀缺性阻碍了从血液中分离DC，因此已经开发出从不同的祖细胞或前体细胞中产生DC的培养方法。事实上，在含有不同生长因子组合的培养中，从骨髓、脐带血或成人血CD34+祖细胞，甚至血单核细胞中获得相对较高数量的DC的可能性--主要基于GM-CSF、TNF-α和IL-4的使用--使研究它们的个体发育、在不同条件下获得的不同类型的DC的特征以及它们是否与单一的分化途径有关。例如，单核细胞甚至巨噬细胞可以根据所使用的细胞因子分化为DC这一发现必须与支持巨噬细胞和DC谱系早期分支的证据相一致，并提出了关于后者谱系的身份的问题。此外，除了髓系树突状细胞外，树突状细胞还起源于淋巴系祖细胞，淋巴样树突状细胞表现出与髓系树突状细胞不同的特性--至少在小鼠身上是这样。从实际的角度来看，有必要确定最合适的细胞因子组合和时间表，以优化来自不同来源的DC的增殖、分化和成熟。此外，由于DC捕获、处理和呈递抗原的能力因其分化/成熟阶段和来源而异，因此似乎有必要定义在特定病理背景下使用哪种类型的DC进行细胞治疗，以便有效和安全地使用。
Dendritic cells (DC) are the most potent antigen-presenting cells: they, only, can prime naive T lymphocytes and even elicit generation of cytotoxic T lymphocytes to soluble antigens. Thus ex vivo antigen-pulsed DC represent a potentially powerful tool to elicit T-cell mediated responses against viral or tumor-associated antigens. Because isolation of DC as such from the blood is hampered by their scarcity, culture methods to generate them from different progenitors or precursors have been developed. Indeed, the possibility of obtaining relatively high numbers of DC from bone marrow, cord blood or adult blood CD34+ progenitors, or even blood monocytes, in cultures with different combinations of growth factors--mainly based on the use of GM-CSF, TNF-alpha and IL-4--has allowed the study of their ontogeny, the characterization of the different types of DC obtained under diverse conditions, and the assessment of whether they relate to a single pathway of differentiation. For example, the finding that monocytes and even macrophages can differentiate into DC depending on the cytokines used has to be reconciled with evidence that supports earlier branching off of the macrophage and DC lineages, and raises questions as to the identity of the latter lineage. Also, besides DC of myeloid origin, DC arise from lymphoid progenitors, and lymphoid DC display different properties than myeloid DC--at least in mice. From a practical point of view, there is a need to define the most appropriate cytokine combinations and schedules to optimize proliferation, differentiation and maturation of DC from different sources. In addition, because the capacity of DC to capture, process and present antigens varies according to their differentiation/maturation stage and origin, it appears necessary to define which type of DC to use for cell therapy in the setting of a given pathology for efficient and safe use.