HIV Skews the Lineage-Defining Transcriptional Profile of Mycobacterium tuberculosis-Specific CD4+ T Cells.
HIV Skews the Lineage-Defining Transcriptional Profile of Mycobacterium tuberculosis-Specific CD4+ T Cells.
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DOI：
10.4049/jimmunol.1502094
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发表时间：
2016-04-01
期刊：
影响因子：
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通讯作者：
Burgers WA
中科院分区：
文献类型：
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作者：
Riou C;Strickland N;Soares AP;Corleis B;Kwon DS;Wherry EJ;Wilkinson RJ;Burgers WA
HIV感染者即使在CD 4严重丧失之前，也有更大的风险患上结核病（TB），这表明HIV改变了能够抑制细菌复制的CD 4 +T细胞功能。对结核分枝杆菌的有效免疫应答可能依赖于平衡的CD 4应答的发展，其中不同的CD 4 +T辅助细胞亚群协同作用以控制感染。为了确定Mtb特异性CD 4 +Th亚群的多样性并确定HIV感染是否影响这种应答，在HIV未感染（n=20）和HIV感染的具有潜伏性TB感染的个体（n = 20）中的Mtb特异性CD 4 +T细胞中测量谱系定义转录因子T-bet、Gata 3、RORγt和Foxp 3的表达。我们的研究结果表明，在体外再刺激5天后，来自健康个体的Mtb特异性CD 4 +T细胞具有表现出由转录因子共表达的特定模式定义的广谱T辅助细胞亚群的能力。这些转录因子谱在HIV感染个体中是偏斜的，与HIV未感染个体相比，T-bethighFoxp 3 + Mtb特异性CD 4 +T细胞的比例显著降低（p=0.002），这种变化与HIV病毒载量（p=0.0007）和血浆TNF-α（p=0.027）呈负相关。我们的数据表明，在T辅助细胞亚群多样性的一个重要的平衡定义的谱系定义的转录因子共表达谱，被破坏的HIV感染，并建议在损害结核病免疫力的作用HIV通过改变结核病特异性的CD 4 +T辅助细胞亚群的平衡。
HIV-infected persons are at greater risk of developing tuberculosis (TB) even before profound CD4 loss occurs, suggesting that HIV alters CD4+T cell functions capable of containing bacterial replication. An effective immune response to Mycobacterium tuberculosis likely relies on the development of a balanced CD4 response, where distinct CD4+T helper subsets act in synergy to control the infection. To define the diversity of Mtb-specific CD4+Th subsets and determine whether HIV infection impacts such responses, the expression of lineage-defining transcription factors T-bet, Gata3, RORγt and Foxp3 was measured in Mtb-specific CD4+T cells in HIV-uninfected (n=20) and HIV-infected individuals (n=20) with latent TB infection. Our results show that upon 5 day restimulation in vitro, Mtb-specific CD4+T cells from healthy individuals have the ability to exhibit a broad spectrum of T helper subsets, defined by specific patterns of transcription factor co-expression. These transcription factor profiles were skewed in HIV-infected individuals where the proportion of T-bethighFoxp3+ Mtb-specific CD4+T cells was significantly decreased (p=0.002) compared to HIV-uninfected individuals, a change that correlated inversely with HIV viral load (p=0.0007) and plasma TNF-α (p=0.027). Our data demonstrate an important balance in T helper subset diversity defined by lineage-defining transcription factor co-expression profiles that is disrupted by HIV infection and suggest a role for HIV in impairing TB immunity by altering the equilibrium of Mtb-specific CD4+T helper subsets.