Hepatic CD1d expression in hepatitis C virus infection and recognition by resident proinflammatory CD1d-reactive T cells
Hepatic CD1d expression in hepatitis C virus infection and recognition by resident proinflammatory CD1d-reactive T cells
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DOI：
10.4049/jimmunol.173.3.2159
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发表时间：
2004-08-01
影响因子：
4.4
通讯作者：
Exley, MA
中科院分区：
文献类型：
--
作者：
Durante-Mangoni, E;Wang, RJ;Exley, MA
CD 161（+）CD 56（+/-）NKT细胞的一个亚群可以识别由CD 1d呈递的糖脂，并积极或消极地调节炎症反应，包括与几种肝炎模型有关的炎症反应。在健康肝脏中，CD 1d的表达水平非常低，但存在大部分的CD 161（+）CD 56（+）NKT细胞。在丙型肝炎病毒（HCV）感染中存在高水平的非经典促炎性肝脏CD 1d反应性T细胞。HCV感染供体门脉纤维化区域附近的肝脏炎症细胞和胆管细胞特异性上调CD 1d。表达最小CD 1d的肝细胞系被肝CD 1d反应性T细胞有效识别，表明这些细胞在疾病中的作用。来自HCV阳性和阴性供体的肝CD 1d反应性T细胞产生大量IFN-γ和一些IL-13，但很少检测到IL-4。我们证实了大量的肝脏CD 161（+）T细胞，较低水平的CD 56（+）T细胞，和少量的经典不变的NKT细胞。然而，肝脏CD 1d反应性并不局限于任何这些人群。我们认为，病毒感染的肝细胞可以处理有效的CD 1d呈递的肝脏Ag（s），由常驻的Th 1肝脏CD 1d反应性T细胞进行监测。这一过程在急性病毒清除中可能是有益的，但在慢性感染中可能导致肝损伤。
A subset of CD161(+)CD56(+/-) NKT cells can recognize glycolipids presented by CD1d and positively or negatively regulate inflammatory responses, including those implicated in several models of hepatitis. CD1d is expressed at very low levels in the healthy liver, but there is a large fraction of CD161(+)CD56(+) NKT cells. There are high levels of nonclassical proinflammatory hepatic CD1d-reactive T cells in hepatitis C virus (HCV) infection. Hepatic inflammatory cells and biliary cells adjacent to portal tract fibrotic areas of HCV-infected donors specifically up-regulated CD1d. A hepatocyte cell line expressing minimal CD1d was efficiently recognized by hepatic CD1d-reactive T cells, suggesting a role for these cells in disease. Hepatic CD1d-reactive T cells from HCV-positive as well as negative donors produced large amounts of IFN-gamma with some IL-13, but only rarely detectable IL-4. We confirmed large numbers of hepatic CD161(+) T cells, lower levels of CD56(+) T cells, and small numbers of classic invariant NKT cells. However, hepatic CD1d-reactivity was not restricted to any of these populations. We suggest virally infected hepatic cells can process potent CD1d-presented liver Ag(s), for surveillance by resident Th1 hepatic CD1d-reactive T cells. This process may be beneficial in acute viral clearance, but in chronic infection could contribute to liver injury.