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人类胸腺上皮细胞表达一种内源性凝集素,即半乳糖凝集素-1,它可与胸腺细胞和T淋巴母细胞上的核心2 O-聚糖结合。

Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells.

作者信息

Baum L G, Pang M, Perillo N L, Wu T, Delegeane A, Uittenbogaart C H, Fukuda M, Seilhamer J J

机构信息

Department of Pathology and Laboratory Medicine, UCLA School of Medicine 90024.

出版信息

J Exp Med. 1995 Mar 1;181(3):877-87. doi: 10.1084/jem.181.3.877.

Abstract

Thymic epithelial cells play a crucial role in the selection of developing thymocytes. Thymocyte-epithelial cell interactions involve a number of adhesion molecules, including members of the integrin and immunoglobulin superfamilies. We found that human thymic epithelial cells synthesize an endogenous lectin, galectin-1, which binds to oligosaccharide ligands on the surface of thymocytes and T lymphoblastoid cells. Binding of T lymphoblastoid cells to thymic epithelial cells was inhibited by antibody to galectin-1 on the epithelial cells, and by two antibodies, T305 and 2B11, that recognize carbohydrate epitopes on the T cell surface glycoproteins CD43 and CD45, respectively. T lymphoblastoid cells and thymocytes bound recombinant galectin-1, as demonstrated by flow cytometric analysis, and lectin binding was completely inhibited in the presence of lactose. The degree of galectin-1 binding to thymocytes correlated with the maturation stage of the cells, as immature thymocytes bound more galectin-1 than did mature thymocytes. Preferential binding of galectin-1 to immature thymocytes may result from regulated expression of preferred oligosaccharide ligands on those cells, since we found that the epitope recognized by the T305 antibody, the core 2 O-glycan structure on CD43, was expressed on cortical, but not medullary cells. The level of expression of the UDP-GlcNAc:Gal beta 1,3GalNAc-R beta 1, 6GlcNAc transferase (core 2 beta 1, 6 GlcNAc transferase, or C2GnT), which creates the core 2 O-glycan structure, correlated with the glycosylation change between cortical and medullary cells. Expression of mRNA encoding the C2GnT was high in subcapsular and cortical thymocytes and low in medullary thymocytes, as demonstrated by in situ hybridization. These results suggest that galectin-1 participates in thymocyte-thymic epithelial cell interactions, and that this interaction may be regulated by expression of relevant oligosaccharide ligands on the thymocyte cell surface.

摘要

胸腺上皮细胞在发育中的胸腺细胞选择过程中发挥着关键作用。胸腺细胞与上皮细胞的相互作用涉及多种黏附分子,包括整合素家族和免疫球蛋白超家族的成员。我们发现人类胸腺上皮细胞可合成一种内源性凝集素——半乳糖凝集素-1,它能与胸腺细胞和T淋巴母细胞表面的寡糖配体结合。上皮细胞上的半乳糖凝集素-1抗体以及分别识别T细胞表面糖蛋白CD43和CD45上碳水化合物表位的两种抗体T305和2B11,均可抑制T淋巴母细胞与胸腺上皮细胞的结合。流式细胞术分析表明,T淋巴母细胞和胸腺细胞能结合重组半乳糖凝集素-1,且在乳糖存在的情况下,凝集素结合被完全抑制。半乳糖凝集素-1与胸腺细胞的结合程度与细胞的成熟阶段相关,因为未成熟胸腺细胞比成熟胸腺细胞结合更多的半乳糖凝集素-1。半乳糖凝集素-1优先与未成熟胸腺细胞结合,可能是由于这些细胞上优先表达的寡糖配体受到调控,因为我们发现T305抗体识别的表位,即CD43上的核心2 O-聚糖结构,在皮质细胞而非髓质细胞上表达。产生核心2 O-聚糖结构的UDP-GlcNAc:Galβ1,3GalNAc-Rβ1,6GlcNAc转移酶(核心2β1,6 GlcNAc转移酶,或C2GnT)的表达水平,与皮质细胞和髓质细胞之间的糖基化变化相关。原位杂交显示,编码C2GnT的mRNA在被膜下和皮质胸腺细胞中高表达,而在髓质胸腺细胞中低表达。这些结果表明,半乳糖凝集素-1参与胸腺细胞与胸腺上皮细胞的相互作用,且这种相互作用可能受胸腺细胞表面相关寡糖配体表达的调控。

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