Caux C, Vanbervliet B, Massacrier C, Dezutter-Dambuyant C, de Saint-Vis B, Jacquet C, Yoneda K, Imamura S, Schmitt D, Banchereau J
Laboratory for Immunological Research, Dardilly, France.
J Exp Med. 1996 Aug 1;184(2):695-706. doi: 10.1084/jem.184.2.695.
Human dendritic cells (DC) can now be generated in vitro in large numbers by culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNF alpha for 12 d. The present study demonstrates that cord blood CD34+ HPC indeed differentiate along two independent DC pathways. At early time points (day 5-7) during the culture, two subsets of DC precursors identified by the exclusive expression of CD1a and CD14 emerge independently. Both precursor subsets mature at day 12-14 into DC with typical morphology and phenotype (CD80, CD83, CD86, CD58, high HLA class II). CD1a+ precursors give rise to cells characterized by the expression of Birbeck granules, the Lag antigen and E-cadherin, three markers specifically expressed on Langerhans cells in the epidermis. In contrast, the CD14+ progenitors mature into CD1a+ DC lacking Birbeck granules, E-cadherin, and Lag antigen but expressing CD2, CD9, CD68, and the coagulation factor XIIIa described in dermal dendritic cells. The two mature DC were equally potent in stimulating allogeneic CD45RA+ naive T cells. Interestingly, the CD14+ precursors, but not the CD1a+ precursors, represent bipotent cells that can be induced to differentiate, in response to M-CSF, into macrophage-like cells, lacking accessory function for T cells. Altogether, these results demonstrate that different pathways of DC development exist: the Langerhans cells and the CD14(+)-derived DC related to dermal DC or circulating blood DC. The physiological relevance of these two pathways of DC development is discussed with regard to their potential in vivo counterparts.
通过在GM-CSF + TNFα存在的条件下培养CD34 +造血祖细胞12天，现在可以在体外大量生成人类树突状细胞（DC）。本研究表明，脐血CD34 +造血祖细胞确实沿着两条独立的DC途径分化。在培养的早期时间点（第5 - 7天），通过CD1a和CD14的排他性表达鉴定出的两个DC前体亚群独立出现。两个前体亚群在第12 - 14天成熟为具有典型形态和表型（CD80、CD83、CD86、CD58、高HLA II类）的DC。CD1a +前体产生的细胞具有伯贝克颗粒、Lag抗原和E-钙黏蛋白的表达特征，这三种标志物在表皮的朗格汉斯细胞上特异性表达。相比之下，CD14 +祖细胞成熟为缺乏伯贝克颗粒、E-钙黏蛋白和Lag抗原但表达CD2、CD9、CD68以及真皮树突状细胞中描述的凝血因子XIIIa的CD1a + DC。这两种成熟的DC在刺激同种异体CD45RA +初始T细胞方面同样有效。有趣的是，CD14 +前体而非CD1a +前体代表双能细胞，响应M-CSF可被诱导分化为缺乏T细胞辅助功能的巨噬细胞样细胞。总之这些结果表明存在不同的DC发育途径：朗格汉斯细胞以及与真皮DC或循环血液DC相关的CD14（+）衍生的DC。讨论了这两种DC发育途径的生理相关性及其在体内可能对应的细胞。
