Spada F M, Borriello F, Sugita M, Watts G F, Koezuka Y, Porcelli S A
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Eur J Immunol. 2000 Dec;30(12):3468-77. doi: 10.1002/1521-4141(2000012)30:12<3468::AID-IMMU3468>3.0.CO;2-C.
CD1d is a key antigen-presenting molecule involved in the selection and activation of a highly conserved T cell subset known as NK T cells. In this study, we analyzed the expression, regulation and function of human CD1d by various antigen-presenting cells (APC) of myeloid origin, including circulating monocytes, monocyte-derived dendritic cells and macrophages. CD1d was expressed as a mature glycoprotein by these cells, and unlike the other members of the human CD1 family its expression was constitutive and was not strongly up-regulated by GM-CSF and IL-4 or a range of other cytokines. Despite their remarkably low surface expression of CD1d, all myeloid lineage cells tested were extremely potent APC for responses of NK T cell clones to the synthetic glycolipid antigen, alpha-galactosyl ceramide. Prominent localization of CD1d to the endocytic system of monocyte lineage cells was observed, and functional studies suggested that this was important for achieving efficient antigen loading onto CD1d. Overall, these results support the view that monocyte lineage cells are important stimulators of CD1d-restricted immune responses, while also underscoring the unique regulation of CD1d expression by these cells.
CD1d是一种关键的抗原呈递分子，参与了对一类高度保守的T细胞亚群（即自然杀伤T细胞，NK T细胞）的选择和激活。在本研究中，我们分析了人CD1d在多种髓系来源的抗原呈递细胞（APC）中的表达、调控及功能，这些细胞包括循环单核细胞、单核细胞衍生的树突状细胞和巨噬细胞。这些细胞将CD1d表达为一种成熟的糖蛋白，与人类CD1家族的其他成员不同，其表达是组成性的，不会被粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素-4（IL-4）或一系列其他细胞因子强烈上调。尽管所检测的所有髓系细胞系细胞表面的CD1d表达水平极低，但它们都是NK T细胞克隆对合成糖脂抗原α-半乳糖神经酰胺反应的极强APC。观察到CD1d在单核细胞系细胞的内吞系统中显著定位，功能研究表明这对于实现CD1d高效加载抗原很重要。总体而言，这些结果支持这样一种观点，即单核细胞系细胞是CD1d限制性免疫反应的重要刺激物，同时也强调了这些细胞对CD1d表达的独特调控。
