Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection.

Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection.
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DOI:
10.1084/jem.20011723
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发表时间:
2002-05-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Bertoletti A
Bertoletti A
中科院分区:
其他
文献类型:
--
作者:
Reignat S;Webster GJ;Brown D;Ogg GS;King A;Seneviratne SL;Dusheiko G;Williams R;Maini MK;Bertoletti A

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在慢性病毒感染中,缺失、无能和一系列功能障碍会影响病毒特异性CD8细胞。在这里,我们描述了在慢性乙肝病毒感染中存在的CD8细胞的低频率群体,它们在面对大量病毒抗原的情况下存活。尽管这些CD8细胞在体内似乎不会施加免疫压力,但它们在体外增殖、溶解并产生抗病毒细胞因子,因此并不具有经典的“耐受性”。它们的特征是人类白细胞抗原/肽四聚体反应性改变,这不能用TCR下调或功能亲和力降低来解释,这种变化可以通过重复刺激逆转。四聚体结合改变的CD8细胞似乎对包膜抗原具有特异性,而对其他乙肝病毒抗原不具有特异性,这表明CD8细胞功能障碍的机制根据单个病毒抗原的抗原形式和呈递方式而有所不同。
Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically “tolerant” since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.
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