Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection.
Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection.
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DOI：
10.1084/jem.20072076
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发表时间：
2008-09-01
影响因子：
15.3
通讯作者：
Maini, Mala K.
中科院分区：
文献类型：
--
作者：
Das, Abhishek;Hoare, Matthew;Davies, Nathan;Lopes, A. Ross;Dunn, Claire;Kennedy, Patrick T. F.;Alexander, Graeme;Finney, Helene;Lawson, Alistair;Plunkett, Fiona J.;Bertoletti, Antonio;Akbar, Arne N.;Maini, Mala K.
慢性B型肝炎病毒（HBV）感染（CH B）的肝脏炎症的特征在于大量非病毒特异性CD 8 T细胞的流入。对这些淋巴细胞的功能能力知之甚少，这可以为这种情况下病毒控制失败和肝损伤的机制提供见解。我们比较了CHB患者和健康供体的总循环和肝内CD 8 T细胞的效应功能。我们证明，无论其抗原特异性如何，CHB患者的CD 8 T细胞在TCR依赖性刺激下产生白细胞介素-2和增殖的能力受损。相反，这些CD 8 T细胞保留了促炎细胞因子干扰素-γ和肿瘤坏死因子-α的产生。这种异常的功能特征部分归因于近端T细胞受体信号分子CD 3 β的下调，并且可以通过转染CD 3 β或补充其表达所需的氨基酸精氨酸在体外得到纠正。我们提供的证据表明，精氨酸在发炎的肝脏微环境中的耗竭是这些缺陷在全球CD 8 T细胞信号传导和功能的潜在机制。这些数据意味着HBV感染肝脏内的极化CD 8 T细胞可能会阻碍增殖性抗病毒效应子功能，同时促进促炎细胞因子环境。
The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little is known about the functional capacity of these lymphocytes, which could provide insights into mechanisms of failure of viral control and liver damage in this setting. We compared the effector function of total circulating and intrahepatic CD8 T cells in CHB patients and healthy donors. We demonstrated that CD8 T cells from CHB patients, regardless of their antigen specificity, were impaired in their ability to produce interleukin-2 and proliferate upon TCR-dependent stimulation. In contrast, these CD8 T cells had preserved production of the proinflammatory cytokines interferon-γ and tumor necrosis factor-α. This aberrant functional profile was partially attributable to down-regulation of the proximal T cell receptor signaling molecule CD3ζ, and could be corrected in vitro by transfection of CD3ζ or replenishment of the amino acid arginine required for its expression. We provide evidence for depletion of arginine in the inflamed hepatic microenvironment as a potential mechanism for these defects in global CD8 T cell signaling and function. These data imply that polarized CD8 T cells within the HBV-infected liver may impede proliferative antiviral effector function, while contributing to the proinflammatory cytokine environment.
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影响因子：
4.4
作者：
Krishnan, S;Kiang, JG;Tsokos, GC
通讯作者：
Tsokos, GC
DOI：
10.1084/jem.20061287
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dunn C;Brunetto M;Reynolds G;Christophides T;Kennedy PT;Lampertico P;Das A;Lopes AR;Borrow P;Williams K;Humphreys E;Afford S;Adams DH;Bertoletti A;Maini MK
通讯作者：
Maini MK
影响因子：
5.4
作者：
Kropf, Pascale;Baud, David;Marshall, Sara E;Munder, Markus;Mosley, Angelina;Fuentes, Jose M;Bangham, Charles R M;Taylor, Graham P;Herath, Shanti;Choi, Beak-San;Soler, German;Teoh, Tg;Modolell, Manuel;Muller, Ingrid
通讯作者：
Muller, Ingrid
DOI：
10.1084/jem.186.9.1407
发表时间：
1997-11-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hamann D;Baars PA;Rep MH;Hooibrink B;Kerkhof-Garde SR;Klein MR;van Lier RA
通讯作者：
van Lier RA
影响因子：
4.4
作者：
Karrer, U;Sierro, S;Klenerman, P
通讯作者：
Klenerman, P