Rosenzwajg M, Canque B, Gluckman J C
Laboratoire de Biologie et Génétiques des Déficits Immunitaires, faculté de Médecine, Paris, France.
Blood. 1996 Jan 15;87(2):535-44.
The most effective antigen-presenting cells for T lymphocytes are dendritic cells (DCs), the differentiation pathway of which, however, is incompletely characterized. We examined here how DCs differentiated from human cord blood CD34+ progenitor cells cultured with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and stem cell factor. After 5 days, 2 of 3 nonadherent cells were CD13hiHLA-DRhiCD4+, half of them were also CD14+, and < or = 10% were CD1a+. When day-5 sorted CD13hiCD1a- and CD13lo cells were further cultured, CD1a+ cells appeared in the already CD13hi population, whereas CD13hi cells, a minority of which rapidly became CD1a+, emerged from the CD13lo population. By day 12, still 66% of bulk cells in suspension were CD13hi, most of which displayed high forward and side scatters of large granular cells. Half of CD13hi cells were CD1a+. All CD13hi cells expressed to the same extent DR, CD4, costimulatory and adhesion molecules, and various amounts of CD14. CD1a+ cells stimulated allogeneic lymphocytes more than CD13hiCD1a- cells and, although they were CD14+, both cell types were nonspecific esterase-negative nonphagocytic cells and were stronger mixed leukocyte reaction stimulators than were their macrophage counterparts. Eventually, the percentage of CD1a+ cells decreased. However, typical CD1a+ DCs still emerged in culture of sorted day-12 CD13hiCD1a- cells, and adding interleukin-4 to bulk cultures at that time led to the persistence of the CD1a+ population while diminishing CD14 expression. Thus, this system results first in the differentiation of CD13hi precursors that strongly express DR and CD4, from which more mature CD1a+ DCs continuously differentiate all along the culture period.
对T淋巴细胞而言，最有效的抗原呈递细胞是树突状细胞（DCs），然而其分化途径尚未完全明确。我们在此研究了DCs如何从用人粒细胞-巨噬细胞集落刺激因子、肿瘤坏死因子-α和干细胞因子培养的人脐血CD34+祖细胞分化而来。5天后，3个非贴壁细胞中有2个是CD13高表达HLA-DR高表达CD4+，其中一半也是CD14+，且≤10%是CD1a+。当对第5天分选的CD13高表达CD1a-和CD13低表达细胞进一步培养时，CD1a+细胞出现在已有的CD13高表达群体中，而CD13高表达细胞（其中少数迅速变为CD1a+）则从CD13低表达群体中出现。到第12天，悬浮的大部分细胞中仍有66%是CD13高表达，其中大多数表现出大颗粒细胞的高前向散射和侧向散射。一半的CD13高表达细胞是CD1a+。所有CD13高表达细胞在相同程度上表达DR、CD4、共刺激分子和黏附分子，以及不同量的CD14。CD1a+细胞比CD13高表达CD1a-细胞更能刺激同种异体淋巴细胞，并且尽管它们是CD14+，但这两种细胞类型都是非特异性酯酶阴性的非吞噬细胞，并且是比其巨噬细胞对应物更强的混合淋巴细胞反应刺激物。最终，CD1a+细胞的百分比下降。然而，典型的CD1a+ DCs仍在分选的第12天CD13高表达CD1a-细胞培养物中出现，并且此时向大量培养物中添加白细胞介素-4会导致CD1a+群体持续存在，同时减少CD14表达。因此，该系统首先导致强烈表达DR和CD4的CD13高表达前体的分化，在整个培养期间，更成熟的CD1a+ DCs不断从这些前体中分化出来。
