Functional and phenotypic characterization of distinct porcine dendritic cells derived from peripheral blood monocytes

Functional and phenotypic characterization of distinct porcine dendritic cells derived from peripheral blood monocytes
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DOI:
10.1046/j.1365-2567.2001.01200.x
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发表时间:
2001-04-01
期刊:
影响因子:
6.4
通讯作者:
Juillard, V
Juillard, V
中科院分区:
医学2区
文献类型:
--
作者:
Paillot, R;Laval, F;Juillard, V

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树突状细胞 (DC) 是骨髓来源的抗原呈递细胞,具有与 T 细胞相互作用并调节其反应的精湛能力。人们对猪 DC 知之甚少,尽管事实上它们代表了旨在调节猪感染抵抗力的策略中的重要靶标,并且可能在移植生物学中具有重要意义。我们直接从用猪粒细胞巨噬细胞集落刺激因子 (GM-CSF) 和白细胞介素 4 (IL-4) 处理的贴壁外周血细胞中产生未成熟的单核细胞来源的猪树突状细胞 (MoDC)。通过电子显微镜观察细胞,并使用单克隆抗体表征其表型。猪 MoDC 的功能得到证实,表明这些细胞能够执行与抗原捕获相关的不同专门功能,并且是初级同种异体混合白细胞反应中的有效刺激剂。用猪细胞系来源的坏死因子处理 MoDC 导致 MoDC 的表型和功能成熟。我们还证实,单核细胞衍生的 DC 受到细胞因子的差异调节,表明转化生长因子-β1 (TGF-β1) 能够将单核细胞前体重定向到呈现典型伯贝克颗粒的朗格汉斯细胞的分化途径。有趣的是,与人类和小鼠模型相反,我们发现单核细胞来源的猪朗格汉斯型细胞 (MoLC) 比不含 TGF-β1 的 MoDC 更有效地激活同种异体 T 细胞。
Dendritic cells (DCs) are bone marrow-derived antigen-presenting cells that have an exquisite capacity to interact with T cells and modulate their responses. Little is known about porcine DCs despite the fact that they represent an important target in strategies that are aimed at modulating resistance to infection in pigs and may be of major importance in transplantation biology. We generated immature monocyte-derived porcine dendritic cells (MoDCs) directly from adherent peripheral blood cells treated with porcine granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The cells were observed via electron microscopy and their phenotype was characterized using monoclonal antibodies. The functionality of the porcine MoDCs was demonstrated showing that the cells were capable of different specialized functions relevant to antigen capture and were potent stimulators in a primary allo-mixed leucocyte reaction. Treatment of the MoDCs with porcine cell line-derived necrotic factors resulted in the phenotypic and functional maturation of MoDCs. We confirmed also that monocyte-derived DCs were differentially regulated by cytokines, showing that transforming growth factor-beta1 (TGF-beta1) is able to redirect monocytic precursors into the differentiation pathway of Langerhans' cells presenting typical Birbeck granules. Interestingly, and in contrast to the human and murine model, we showed that the monocyte-derived porcine Langerhans'-type cells (MoLCs) were much more potent activators of allogeneic T cells than MoDCs obtained without TGF-beta1.