Department of Clinical Immunology & Rheumatology, Academic Medical Center, Amsterdam, the Netherlands.
PLoS Pathog. 2012 Sep;8(9):e1002889. doi: 10.1371/journal.ppat.1002889. Epub 2012 Sep 27.
CD8(+) T-cell responses against latent viruses can cover considerable portions of the CD8(+) T-cell compartment for many decades, yet their initiation and maintenance remains poorly characterized in humans. A key question is whether the clonal repertoire that is raised during the initial antiviral response can be maintained over these long periods. To investigate this we combined next-generation sequencing of the T-cell receptor repertoire with tetramer-sorting to identify, quantify and longitudinally follow virus-specific clones within the CD8(+) T-cell compartment. Using this approach we studied primary infections of human cytomegalovirus (hCMV) and Epstein Barr virus (EBV) in renal transplant recipients. For both viruses we found that nearly all virus-specific CD8(+) T-cell clones that appeared during the early phase of infection were maintained at high frequencies during the 5-year follow-up and hardly any new anti-viral clones appeared. Both in transplant recipients and in healthy carriers the clones specific for these latent viruses were highly dominant within the CD8(+) T-cell receptor Vβ repertoire. These findings suggest that the initial antiviral response in humans is maintained in a stable fashion without signs of contraction or changes of the clonal repertoire.
CD8(+) T 细胞对潜伏病毒的反应可以覆盖 CD8(+) T 细胞区室的相当大部分长达数十年，但它们的起始和维持在人类中仍未得到很好的描述。一个关键问题是，在最初的抗病毒反应中产生的克隆谱是否可以在这些长时期内维持。为了研究这一点，我们结合了 T 细胞受体谱的下一代测序和四聚体分选，以鉴定、定量和纵向跟踪 CD8(+) T 细胞区室中的病毒特异性克隆。使用这种方法，我们研究了肾移植受者中人类巨细胞病毒 (hCMV) 和 Epstein Barr 病毒 (EBV) 的原发性感染。对于这两种病毒，我们发现感染早期出现的几乎所有病毒特异性 CD8(+) T 细胞克隆在 5 年的随访中都以高频率维持，几乎没有新的抗病毒克隆出现。在移植受者和健康携带者中，这些潜伏病毒特异性的克隆在 CD8(+) T 细胞受体 Vβ 谱中高度占主导地位。这些发现表明，人类的初始抗病毒反应以稳定的方式维持，没有收缩或克隆谱变化的迹象。
