Role of CD8+ T Cells in The Pathogenesis of HIV Disease

CD 8 + T细胞对于有效的宿主防御病毒感染至关重要。先前针对感染个体中人类免疫缺陷病毒（HIV）诱导的免疫应答的研究表明，CD 8 + T细胞在控制病毒复制中起重要作用。然而，尽管HIV特异性CD 8 + T细胞丰富，但在缺乏有效抗逆转录病毒治疗的情况下，大多数HIV感染者中不包含病毒复制。活跃的HIV复制与许多免疫学变化相关，其中最显著和一致的是表达CD 38的CD 8 + T细胞的增加。先前的研究已经证明，CD 8 + T细胞上的CD 38表达与具有可检测的血浆病毒血症的感染个体的不良预后结果相关;然而，CD 38的表达与HIV特异性CD 8 + T细胞的频率之间的关系尚不清楚。在本研究中，我们证明了HIV特异性CD 8 + T细胞水平与未治疗的HIV感染者中表达CD 38的CD 8 + T细胞百分比之间的直接相关性。HIV特异性CD 8 + T细胞在表达CD 38的CD 8 + T细胞百分比较低的患者中均匀分布在CD 38-CD 8+和CD 38 + CD 8 + T细胞之间，而在表达CD 38的CD 8 + T细胞百分比较高的患者中，其分布偏向于CD 38 + CD 8 + T细胞群体。此外，在CD 38 + CD 8 + T细胞群中发现的HIV特异性CD 8 + T细胞的频率与表达CD 38的CD 8 + T细胞的百分比之间观察到直接相关性。我们的数据表明，在病毒复制活跃的感染个体中，CD 38 + CD 8 + T细胞群中存在的相当大比例的HIV特异性CD 8 + T细胞是由HIV驱动的异常免疫激活引起的，并且可能不表现出对感染靶点的有效细胞溶解活性，从而解释了为什么HIV不能成功地被这些个体中的CD 8 + T细胞所包含。因此，表达CD 38的HIV特异性CD 8 + T细胞的大比例可能反映了HIV感染个体中有缺陷的病毒特异性免疫应答。

CD8+ T cells are critical for effective host defenses against viral infections. Previous studies addressing human immunodeficiency virus (HIV)-induced immune responses in infected individuals have suggested that CD8+ T cells play an important role in controlling viral replication. However, despite an abundance of HIV-specific CD8+ T cells, viral replication is not contained in the majority of HIV-infected individuals in the absence of effective antiretroviral therapy. Active HIV replication is associated with numerous immunologic changes, most notable and consistent of which is an increase in CD8+ T cells expressing CD38. Previous studies have demonstrated that the expression of CD38 on CD8+ T cells is associated with poor prognostic outcome in infected individuals with detectable plasma viremia; however, the relationship between the expression of CD38 and the frequency of HIV-specific CD8+ T cells is unclear. In the present study, we demonstrate a direct correlation between the level of HIV-specific CD8+ T cells and the percentage of CD8+ T cells expressing CD38 in untreated HIV-infected individuals. HIV-specific CD8+ T cells were shown to be evenly distributed between CD38-CD8+ and CD38+CD8+ T cells in patients with a low percentage of CD8+ T cells expressing CD38 whereas their distribution was skewed toward the CD38+CD8+ T cell population in patients with a high percentage of CD8+ T cells expressing CD38. In addition, a direct correlation was observed between the frequency of HIV-specific CD8+ T cells that were found in the CD38+CD8+ T cell population and the percentage of CD8+ T cells expressing CD38. Our data suggest that a substantial proportion of the HIV-specific CD8+ T cells present in the population of CD38+CD8+ T cells in infected individuals with active viral replication arise by HIV-driven aberrant immune activation and may not manifest effective cytolytic activitiy against infected targets, thus providing an explanation why HIV is not successfully contained by CD8+ T cells in such individuals. Therefore, the large proportion of HIV-specific CD8+ T cells that express CD38 may reflect a defective virus-specific immune response in HIV-infected individuals.