Distinct CD4+ CD8+ double-positive T cells in the blood and liver of patients during chronic hepatitis B and C.

Distinct CD4+ CD8+ double-positive T cells in the blood and liver of patients during chronic hepatitis B and C.
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慢性丙型肝炎和C中患者的血液和肝脏中不同的CD4+ CD8+双阳性T细胞。

DOI:
10.1371/journal.pone.0020145
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Saunier B
Saunier B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nascimbeni M;Pol S;Saunier B

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CD4+和CD8+T细胞是适应性细胞免疫反应的主要效应者,在胸腺中与未成熟的、无功能的CD4+CD8+双阳性T细胞(DPT)相区别。在急性病毒感染期间,已观察到循环中DPT淋巴细胞比例的增加;在慢性病毒疾病中,胸腺外DPT细胞的作用和重新分配在很大程度上仍未确定。我们对慢性感染丙型肝炎病毒(丙型肝炎病毒)或乙型肝炎病毒(乙肝病毒)患者的血液和肝脏中的DPT细胞进行了表型分析。丙型肝炎病毒感染者的DPT细胞比例最高,以CD4高CD8为主,而乙肝病毒感染者多表现为CD4低CD8高和CD4高CD8高的DPT细胞。DPT细胞在肝脏中的比例高于在血液中的比例,对于上述每个亚群,它们在这两个隔室中的频率之间存在相关性。在丙型肝炎患者中,肝内DPT细胞表现出比血液中更多的异质性激活、分化和记忆表型;它们大多表达胸腺T细胞发育的标志CD1a。在体外,用细胞培养产生的丙型肝炎病毒接种肝脏切片时,伴随着CD8高表达细胞的消失,提示该病毒对肝脏DPT细胞的表型有直接影响。我们的结果表明,在一半的患者中,慢性丙型肝炎病毒感染促进了DPT细胞的产生,可能是通过胸腺的重新诱导和肝脏的选择。
CD4+ and CD8+ T cells, the main effectors of adaptive cellular immune responses, differentiate from immature, non-functional CD4+CD8+ double-positive T (DPT) cells in the thymus. Increased proportions of circulating DPT lymphocytes have been observed during acute viral infections; in chronic viral diseases, the role and repartition of extra-thymic DPT cells remain largely uncharacterized. We performed a phenotypic analysis of DPT cells in blood and liver from patients chronically infected by hepatitis C (HCV) or B (HBV) viruses. The highest percentages of DPT cells, predominantly CD4highCD8low, were observed in patients infected by HCV, while HBV-infected patients mostly displayed CD4lowCD8high and CD4highCD8high DPT cells. All proportions of DPT cells were higher in liver than in blood with, for each subpopulation referred to above, a correlation between their frequencies in these two compartments. In HCV patients, intra-hepatic DPT cells displayed more heterogeneous activation, differentiation and memory phenotypes than in the blood; most of them expressed CD1a, a marker of T cell development in the thymus. Ex vivo, the inoculation of liver slices with HCV produced in cell culture was accompanied by a disappearance of CD8high cells, suggesting a direct effect of the virus on the phenotype of DPT cells in the liver. Our results suggest that, in half of the patients, chronic HCV infection promotes the production of DPT cells, perhaps by their re-induction in the thymus and selection in the liver.
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