Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia
Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia
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DOI：
10.1128/jvi.00438-15
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发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Streeck, Hendrik
中科院分区：
文献类型：
--
作者：
Johnson, Susan;Eller, Michael;Streeck, Hendrik
CD4（+）T细胞在慢性病毒感染的控制中起着关键作用。最近，非传统的CD4（+）T细胞的功能已经超出了辅助作用，并已提出了细胞溶解性CD4（+）T细胞在控制HIV感染中的作用。我们在这里定义的转录，表型和功能的艾滋病毒特异性溶细胞性CD4（+）T细胞。对HIV特异性溶细胞性CD4（+）T细胞的Fluidigm BioMark和多参数流式细胞术分析显示，与Th1 CD4（+）细胞相比，其转录特征不同，但与HIV特异性溶细胞性CD8（+）T细胞具有相似的特征。此外，HIV特异性溶细胞性CD4（+）T细胞显示出与HIV特异性CD8（+）T细胞相当的杀伤活性，并在消除病毒感染细胞方面协同工作。有趣的是，我们发现溶细胞性CD4（+）T细胞在急性HIV感染早期出现，并紧密跟随急性病毒载量轨迹。这种出现与早期病毒设定点有关，表明尽管CD4 T细胞对HIV感染易感，但仍参与早期控制。我们的数据表明，溶细胞性CD4（+）T细胞作为一个独立的亚群，不同于Th1细胞，显示与CD8（+）T细胞在长期控制HIV infection.IMPORTANCEThe免疫系统的能力，以控制慢性HIV感染是疫苗设计和治疗方法的关键利益。许多研究都集中在CD8（+）T细胞控制病毒的能力的影响上，而CD4（+）T细胞作为HIV控制中的效应子被忽视，因为它们优先被感染。我们在这里显示，HIV特异性CD4（+）T细胞的一个子集在HIV复制的细胞溶解控制合作。此外，这些细胞代表CD4（+）T细胞的独特亚群，与HIV特异性Th1细胞相比显示出显著的转录和表型差异，但与CD8+ T细胞相似。这些发现对于我们理解HIV免疫病理学非常重要。
CD4(+) T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4(+) T cell functions beyond helper effects have been described, and a role for cytolytic CD4(+) T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4(+) T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4(+) T cells revealed a distinct transcriptional signature compared to Th1 CD4(+) cells but shared similar features with HIV-specific cytolytic CD8(+) T cells. Furthermore, HIV-specific cytolytic CD4(+) T cells showed comparable killing activity relative to HIV-specific CD8(+) T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4(+) T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4(+) T cells as an independent subset distinct from Th1 cells that show combined activity with CD8(+) T cells in the long-term control of HIV infection.IMPORTANCEThe ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8(+) T cells to control the virus, while CD4(+) T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4(+) T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4(+) T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology.