CD8low CD100- T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection
CD8low CD100- T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection
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CD8(低) CD100(-) T 细胞识别出与人汉坦病毒感染期间病毒控制相关的新型 CD8 T 细胞亚群
DOI：
10.1128/jvi.01610-15
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发表时间：
2015-12-01
影响因子：
5.4
通讯作者：
Jin, Boquan
中科院分区：
文献类型：
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作者：
Liu, Bei;Ma, Ying;Jin, Boquan
汉滩病毒（HTNV）感染可引起人类严重致死性肾综合征出血热（HFRS）。CD 8（+）T细胞在对抗HTNV感染中起着关键作用。然而，不同的CD 8（+）T细胞亚群对抗病毒感染的免疫应答的贡献知之甚少。在这里，我们在HFRS患者中鉴定了一种新的CD 8（+）T细胞亚群，其特征是CD 8（低）CD 100（-）表型。在HFRS早期，CD 8（low）CD 100（-）亚群占CD 8（+）T细胞总数的中位数为14.3%，在感染晚期，这一百分比随后下降，而健康对照组中不存在这一亚群。此外，CD 8（低）CD 100（+）细胞与高活化相关，表达高水平的细胞溶解效应分子，并表现出效应CD 8（+）T细胞（CCR 7（+/-）CD 45 RA（-）CD 127（高）CD 27（int）CD 28（低）CD 62 L（-））的独特表达谱。当用特异性HTNV核衣壳蛋白衍生肽库刺激时，大多数应答的CD 8（+）细胞（γ干扰素[IFN-γ]阳性和/或肿瘤坏死因子α [TNF-α]阳性）是CD 8（低）CD 100-细胞。HTNV特异性CD 8（+）T细胞中CD 8低CD 100（-）细胞的频率在轻度病例中高于较重度病例。CD 8（low）CD 100（-）细胞在HFRS早期CD 8（+）T细胞中的比例与HTNV病毒载量呈负相关，提示CD 8（low）CD 100（-）细胞可能与病毒清除有关。感染晚期CD 8（低）CD 100（-）亚群的收缩可能与PD-1的持续高表达水平有关。这些结果可能为我们理解CD 8（+）T细胞介导的保护性免疫以及HTNV感染后的免疫稳态提供新的见解。重要意义CD 8（+）T细胞在抗病毒免疫应答中起重要作用。结果发现，HFRS患者CD 8（low）CD 100（-）细胞占CD 8（+）T细胞的比例与HTNV病毒载量呈负相关，且轻症患者CD 8（low）CD 100（-）细胞占病毒特异性CD 8（+）T细胞的比例高于重症患者。这些结果暗示了CD 8（低）CD 100（-）细胞亚群在人类HTNV感染期间的病毒控制中的有益作用。
Hantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8(+) T cells play a critical role in combating HTNV infections. However, the contributions of different CD8(+) T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8(+) T cells characterized by the CD8(low) CD100(-) phenotype in HFRS patients. The CD8(low) CD100(-) subset accounted for a median of 14.3% of the total CD8(+) T cells in early phase of HFRS, and this percentage subsequently declined in the late phase of infection, whereas this subset was absent in healthy controls. Furthermore, the CD8(low) CD100(+) cells were associated with high activation and expressed high levels of cytolytic effector molecules and exhibited a distinct expression profile of effector CD8(+) T cells (CCR7(+/-) CD45RA(-) CD127(high) CD27(int) CD28(low) CD62L(-)). When stimulated with specific HTNV nucleocapsid protein-derived peptide pools, most responding CD8(+) cells (gamma interferon [IFN-gamma] positive and/or tumor necrosis factor alpha [TNF-alpha] positive) were CD8(low) CD100- cells. The frequency of CD8low CD100(-) cells among HTNV-specific CD8(+) T cells was higher in milder cases than in more severe cases. Importantly, the proportion of the CD8(low) CD100(-) subset among CD8(+) T cells in early phase of HFRS was negatively correlated with the HTNV viral load, suggesting that CD8(low) CD100(-) cells may be associated with viral clearance. The contraction of the CD8(low) CD100(-) subset in late phase of infection may be related to the consistently high expression levels of PD-1. These results may provide new insights into our understanding of CD8(+) T cell-mediated protective immunity as well as immune homeostasis after HTNV infection in humans.IMPORTANCE CD8(+) T cells play important roles in the antiviral immune response. We found that the proportion of CD8(low) CD100(-) cells among CD8(+) T cells from HFRS patients was negatively correlated with the HTNV viral load, and the frequency of CD8(low) CD100(-) cells among virus-specific CD8(+) T cells was higher in milder HFRS cases than in more severe cases. These results imply a beneficial role for the CD8(low) CD100(-) cell subset in viral control during human HTNV infection.