Liver sinusoidal endothelial cells are insufficient to activate T cells
Liver sinusoidal endothelial cells are insufficient to activate T cells
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DOI：
10.4049/jimmunol.173.1.230
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发表时间：
2004-07-01
影响因子：
4.4
通讯作者：
DeMatteo, RP
中科院分区：
文献类型：
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作者：
Katz, SC;Pillarisetty, VG;DeMatteo, RP
肝窦内皮细胞(LSEC)表达MHCⅡ类分子、CD80、CD86和CD11c，能有效刺激初始T细胞。由于已知树突状细胞(DC)具有这些特征，我们试图直接比较小鼠LSEC和DC的表型和功能。用胶原酶消化C57BL/6小鼠肝脏，密度梯度离心法获得非实质细胞。从浓缩的非实质细胞组分中，用免疫磁珠分离LSEC(CD45(-))，纯度达到99%。流式细胞仪分析显示CD31、von Willebrand因子和FcGammaRs在LSEC中高表达。但与DC不同的是，LSEC低表达或不表达MHC-11、CD86和CD11c。LSEC在体外和体内均表现出较高的摄取Ag能力。虽然乙酰化低密度脂蛋白的摄取被认为是LSEC的一种特殊功能，但我们在体内发现DC捕获乙酰化低密度脂蛋白的程度类似。与其表型一致，LSEC是同种异体T细胞的弱刺激因子。此外，在没有外源性共刺激的情况下，LSEC诱导的CD4(+)或CD8(+)TCR转基因T细胞的增殖可以忽略不计。因此，与以前的报告相反，我们的数据表明，LSEC本身不足以激活初始T细胞。
Liver sinusoidal endothelial cells (LSEC) have been reported to express MHC class II, CD80, CD86, and CD11c and effectively stimulate naive T cells. Because dendritic cells (DC) are known to possess these characteristics, we sought to directly compare the phenotype and function of murine LSEC and DC. Nonparenchymal cells from C57BL/6 mice were obtained by collagenase digestion of the liver followed by density gradient centrifugation. From the enriched nonparenchymal cell fraction, LSEC (CD45(-)) were then isolated to 99% purity using immunomagnetic beads. Flow cytometric analysis of LSEC demonstrated high expression of CD31, von Willebrand factor, and FcgammaRs. However, unlike DC, LSEC had low or absent expression of MHC class 11, CD86, and CD11c. LSEC demonstrated a high capacity for Ag uptake in vitro and in vivo. Although acetylated low-density lipoprotein uptake has been purported to be a specific function of LSEC, we found DC captured acetylated low-density lipoprotein to a similar extent in vivo. Consistent with their phenotype, LSEC were poor stimulators of allogeneic T cells. Furthermore, in the absence of exogenous costimulation, LSEC induced negligible proliferation of CD4(+) or CD8(+) TCR-transgenic T cells. Thus, contrary to previous reports, our data indicate that LSEC alone are insufficient to activate naive T cells.