Dendritic cells and immune-based therapies.
Dendritic cells and immune-based therapies.
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DOI：
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发表时间：
1996-07
影响因子：
2.6
通讯作者：
Steinman Rm
中科院分区：
文献类型：
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作者：
Steinman Rm
白细胞的树突状细胞 (DC) 谱系专门捕获抗原并刺激 T 依赖性免疫。由于 DC 无需其他佐剂即可在体内诱导 T 细胞反应，因此可被视为“天然佐剂”。 DC 是最不丰富的白细胞，但产生大量 DC 的方法正在开发中。体外，DC 由在粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 和肿瘤坏死因子-α (TNF-α) 组合存在下培养的 CD34+ 祖细胞发育而来。此类工作激发了人们对向 DC 充电临床相关抗原并诱导患者主动免疫的兴趣。将抗原靶向 DC 也可能变得可行，因为识别出不同的抗原受体，例如 DEC-205，一种具有 10 个连续 C 型凝集素结构域的 DECalectin。 DEC-205 可以介导 DC 的吸附吸收和呈现。艾滋病是另一种在设计新疗法时应考虑 DC 的疾病，因为 DC 在促进 HIV-1 复制方面发挥着重要作用。许多 HIV-1 分离株诱导 DC 和 CD4+ 记忆 T 细胞之间的合胞体。这些合胞体反过来又是 HIV-1 有效感染的场所，可能是因为必需的转录因子（如 NF-kappaB 和 Sp1）分别由 DC 和 T 细胞分别提供。对 DC 谱系的进一步关注应该为在多种临床环境中操纵免疫系统提供新的途径。
The dendritic cell (DC) lineage of white blood cells specializes in capturing antigens and stimulating T-dependent immunity. Because of their efficacy in inducing T cell responses in vivo without other adjuvants, DCs can be considered "nature's adjuvant." DCs are the least abundant of leukocytes, but methods for generating large numbers of DCs are being developed. Ex vivo, DCs develop from CD34+ progenitors cultured in the presence of a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha). This kind of work is stimulating interest in charging DCs with clinically relevant antigens and inducing active immunity in patients. Targeting antigens to DCs may become feasible also because of the identification of distinct antigen receptors such as DEC-205, a DECalectin with 10 contiguous, C-type lectin domains. DEC-205 can mediate adsorptive uptake and presentation via DCs. AIDS is another disease for which DCs should be considered in designing new therapies, since DCs can play a major role in promoting HIV-1 replication. Many HIV-1 isolates induce syncytia between DCs and CD4+ memory T cells. These syncytia in turn are the site for a productive infection with HIV-1, possibly because requisite transcription factors like NF-kappaB and Sp1 are separately provided by DCs and T cells, respectively. Further attention to the DC lineage should provide new avenues for manipulating the immune system in several clinical contexts.