HLA-B7-Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis
HLA-B7-Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis
复制标题
DOI：
10.4049/jimmunol.1103100
复制
发表时间：
2012-05-01
影响因子：
4.4
通讯作者：
Du Pasquier, Renaud A.
中科院分区：
文献类型：
--
作者：
Jilek, Samantha;Schluep, Myriam;Du Pasquier, Renaud A.
据推测，EB病毒特异性CD 8（+）T细胞反应可能在多发性硬化症（MS）患者中失调，可能导致对这种病毒的次优控制。为了更详细地检测CD 8（+）T细胞应答，我们使用四聚体分析了大量MS患者和对照受试者中HLA-A2-、HLA-B7-和HLA-B8限制的EBV和CMV特异性CD 8（+）T细胞应答。评估了EBV和CMV特异性CD 8（+）T细胞的溶细胞颗粒含量以及细胞毒活性。我们发现MS患者HLA-A2和HLA-B7的患病率分别较低或较高。在HLA-B7（+）MS患者中使用HLA I类四聚体，具有HLA-B*0702/EBVRPP特异性CD 8（+）T细胞的MS患者的患病率较高。然而，HLA-B*0702/EBVRPP特异性和HLA-B*0702/CMVTPR特异性CD 8（+）T细胞应答的幅度（即，在MS患者中，携带对给定表位特异性的CD 8（+）T细胞的研究对象中四聚体（+）CD 8（+）T细胞的百分比较低。使用其他四聚体没有发现差异。在用HLA-B *0702/EBVRPP肽刺激后，IL-2、穿孔素和颗粒酶B的产生以及HLA-B *0702/EBVRPP特异性CD 8（+）T细胞的细胞毒性降低。总之，我们的研究结果表明，HLA-B*0702限制性病毒（特别是EBV）特异性CD 8（+）T细胞反应在MS患者中失调。该观察是特别有趣的，已知HLA-B7等位基因在MS患者中更频繁地表达并且考虑到EBV与MS相关。The Journal of Immunology，2012，188：4671-4680。
It was hypothesized that the EBV-specific CD8(+) T cell response may be dysregulated in multiple sclerosis (MS) patients, possibly leading to a suboptimal control of this virus. To examine the CD8(+) T cell response in greater detail, we analyzed the HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and CMV-specific CD8(+) T cell responses in a high number of MS patients and control subjects using tetramers. Content in cytolytic granules, as well as cytotoxic activity, of EBV- and CMV-specific CD8(+) T cells was assessed. We found that MS patients had a lower or a higher prevalence of HLA-A2 and HLA-B7, respectively. Using HLA class I tetramers in HLA-B7(+) MS patients, there was a higher prevalence of MS patients with HLA-B*0702/EBVRPP-specific CD8(+) T cells ex vivo. However, the magnitude of the HLA-B*0702/EBVRPP-specific and HLA-B*0702/CMVTPR-specific CD8(+) T cell response (i.e., the percentage of tetramer(+) CD8(+) T cells in a study subject harboring CD8(+) T cells specific for the given epitope) was lower in MS patients. No differences were found using other tetramers. After stimulation with the HLA-B*0702/EBVRPP peptide, the production of IL-2, perforin, and granzyme B and the cytotoxicity of HLA-B*0702/EBVRPP-specific CD8(+) T cells were decreased. Altogether, our findings suggest that the HLA-B*0702-restricted viral (in particular the EBV one)-specific CD8(+) T cell response is dysregulated in MS patients. This observation is particularly interesting knowing that the HLA-B7 allele is more frequently expressed in MS patients and considering that EBV is associated with MS. The Journal of Immunology, 2012, 188: 4671-4680.