Overview of the cellular immunity against JC virus in progressive multifocal leukoencephalopathy
Overview of the cellular immunity against JC virus in progressive multifocal leukoencephalopathy
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DOI：
10.1080/13550280290167894
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发表时间：
2002-12-01
影响因子：
3.2
通讯作者：
Koralnik, IJ
中科院分区：
文献类型：
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作者：
Koralnik, IJ
人类多瘤病毒JC（JCV）感染大多数健康成年人而不引起任何疾病。在细胞介导的免疫力严重缺陷的情况下，例如在获得性免疫缺陷综合征（AIDS）、恶性肿瘤或器官移植受者中，JCV可重新激活并引起进行性多灶性白质脑病（PML），这是一种致命的中枢神经系统脱髓鞘疾病。通过血液中病毒特异性免疫球蛋白G（IgG）的存在或通过脑脊液（CSF）中IgG的鞘内合成来测量的体液免疫应答无法控制PML的进展。CD 4 + T淋巴细胞识别细胞外病毒蛋白，这些蛋白已通过外源性途径降解为肽，并在抗原呈递细胞表面的主要组织相容性复合体（MHC）II类分子上呈递。与其潜在的免疫抑制一致，PML患者中CD 4 + T淋巴细胞对有丝分裂原或JCV抗原的增殖反应降低。CD 8+细胞毒性T淋巴细胞识别细胞内合成的病毒蛋白，这些蛋白已通过内源性途径降解为肽，并呈递在病毒感染细胞表面的MHC I类分子上。这种JCV肽之一，VP 1（p100）ILMWEAVTL，已被表征为HLA-A*0201+PML存活者中的细胞毒性T淋巴细胞（CTL）表位。用相应的A*0201/JCV VP 1（p100）四聚体复合物染色显示，5/7（71%）PML存活者的VP 1（p100）刺激的外周血单个核细胞（PBMC）具有JCV特异性CTL，而6例PML进展者中没有（P= 0.02）。因此，这种细胞免疫应答可能在预防PML疾病进展中至关重要，四聚体染色试验可用作这些患者临床管理中的预后标志物。
The human polyomavirus JC (JCV) infects most healthy adults without causing any disease. In the setting of severe deficit of cell-mediated immunity, such as in acquired immunodeficiency syndrome (AIDS), malignancies or in organ transplant recipients, JCV can reactivate and cause progressive multifocal leukoencephalopathy (PML), a deadly demyelinating disease of the central nervous system. The humoral immune response, measured by the presence of virus-specific immunoglobulin G (IgG) in the blood or by intrathecal synthesis of IgG in the cerebrospinal fluid (CSF), is unable to contain the progression of PML. CD4+ T lymphocytes recognize extracellular viral proteins that have been degraded into peptides through the exogenous pathway and presented on major histocompatibility complex (MHC) class II molecules at the surface of antigen-presenting cells. Consistent with their underlying immunosuppression, the proliferative response of CD4+ T lymphocytes to mitogens or JCV antigens is reduced in PML patients. CD8+ cytotoxic T lymphocytes recognize intracellularly synthesized viral proteins that have been degraded into peptides through the endogenous pathway, and presented on MHC class I molecules at the surface of virus-infected cells. One of such JCV peptide, the VP1(p100) ILMWEAVTL, has been characterized as a cytotoxic T lymphocyte (CTL) epitope in HLA-A*0201+PML survivors. Staining with the corresponding A*0201/JCV VP1(p100) tetrameric complex showed that VP1(p100)-stimulated peripheral blood mononuclear cells (PBMCs) of 5/7 (71%) PML survivors had JCV-specific CTL, versus none of 6 PML progressors (P=.02). This cellular immune response may therefore be crucial in the prevention of PML disease progression and the tetramer staining assay may be used as a prognostic marker in the clinical management of these patients.