Le Friec Gaëlle, Gros Frédéric, Sebti Yasmine, Guilloux Valérie, Pangault Céline, Fauchet Renée, Amiot Laurence
Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, UPRES EA 22-33, 2 Avenue du Professeur Léon Bernard, CS34317, 35043 Rennes Cedex, France.
J Leukoc Biol. 2004 Dec;76(6):1125-33. doi: 10.1189/jlb.0104015. Epub 2004 Aug 26.
Human leukocyte antigen (HLA-G), a class Ib major histocompatibility complex molecule, is potentially relevant in the immune response through its various immune cell functions. Its expression noticed in some malignancies has also been shown on macrophages and dendritic cells (DC) in tumoral and inflammatory diseases. As DC constitute a key component in the immune response, this work aimed at assessing the expression of HLA-G at transcriptional and proteic levels during differentiation and maturation of the different DC subsets. We show that HLA-G transcription was induced during CD34+-derived DC differentiation and is associated with a cell-surface expression in half of cases and with a substantial secretion of soluble HLA-G in all cases. Results were very similar for monocyte-derived DC, but there was still a weak HLA-G cell-surface expression and a lower level of secretion. On the contrary, HLA-G transcription was weak in plasmacytoid DC without any HLA-G cell-surface expression and with a basal level of secretion. The mechanisms involved in HLA-G expression appear transcriptional and post-transcriptional. However, the amount of HLA-G transcripts and the expression of the protein are not related. HLA-G expression or secretion by DC may have negative consequences on the function of effective immune cells and also on DC themselves via the interaction with inhibitory receptors expressed by these cells. The capacity of DC to express or secrete HLA-G should be studied in the context of cellular therapy using DC in addition to its suppressive action in immune response.
人类白细胞抗原(HLA - G)是一种Ib类主要组织相容性复合体分子,通过其多种免疫细胞功能在免疫反应中具有潜在相关性。在某些恶性肿瘤中观察到的其表达,在肿瘤性疾病和炎症性疾病的巨噬细胞和树突状细胞(DC)上也有显示。由于DC是免疫反应的关键组成部分,这项工作旨在评估不同DC亚群分化和成熟过程中HLA - G在转录水平和蛋白质水平的表达。我们发现,在CD34⁺来源的DC分化过程中HLA - G转录被诱导,在半数情况下与细胞表面表达相关,在所有情况下都与可溶性HLA - G的大量分泌相关。单核细胞来源的DC结果非常相似,但仍有较弱的HLA - G细胞表面表达和较低水平的分泌。相反,浆细胞样DC中HLA - G转录较弱,没有任何HLA - G细胞表面表达且分泌处于基础水平。HLA - G表达所涉及的机制似乎是转录和转录后水平的。然而,HLA - G转录本的量与蛋白质的表达无关。DC表达或分泌HLA - G可能对有效免疫细胞的功能以及通过与这些细胞表达的抑制性受体相互作用对DC自身产生负面影响。除了其在免疫反应中的抑制作用外,在使用DC的细胞治疗背景下,还应研究DC表达或分泌HLA - G的能力。