HIV 免疫激活导致记忆性 CD8 T 细胞中 Eomes 表达增加，与 CD127 的转录下调有关。
HIV immune activation drives increased Eomes expression in memory CD8 T cells in association with transcriptional downregulation of CD127.
机构信息
aCMRS/Laboratory of Immunoregulation, NIAID bExperimental Immunology Branch, NCI, NIH, Bethesda cLaboratory of Molecular Immunoregulation, NCI, NIH, Frederick dBiostatistics Research Branch, NIAID, NIH, Bethesda eCollaborative Clinical Research Branch, NIAID, NIH, Frederick, Maryland, USA.
出版信息
AIDS. 2013 Jul 31;27(12):1867-77. doi: 10.1097/QAD.0b013e3283618487.
BACKGROUND
During HIV infection distinct mechanisms drive immune activation of the CD4 and CD8 T cells leading to CD4 T-cell depletion and expansion of the CD8 T-cell pool. This immune activation is polyclonal and extends beyond HIV-specific T cells. One consequence of this immune activation is a profound decrease in IL-7Rα (CD127) expression on memory CD8 T cells. The mechanisms leading to this are unknown and because of the potential impact of reduced IL-7 signaling in memory T cells specific to HIV and other pathogens, in the present study we examined the molecular mechanisms implicated in this downregulation of CD127.
METHODS
Membrane bound (mIL7RA) and soluble (sIL7RA) mRNA expression was determined by qRT-PCR. CD127, Eomesodermin (Eomes) and T-bet expression in healthy controls and HIV-infected patients were studied by flow cytometry.
RESULTS
CD127 downregulation occurs at the transcriptional level for both mIL7RA and sIL7RA alternative spliced forms in the CD127 memory CD8 T cells. CD127 memory CD8 T cells exhibited increased Eomes expression and an 'effector-like' gene profile. These changes were associated with higher HIV-RNA levels. Following combination antiretroviral therapy (cART), there was an increase in CD127 expression over an extended period of time (>5 months) which was associated with decreased Eomes expression.
CONCLUSION
CD127 is downregulated at a transcriptional level in memory CD8 T cells in association with upregulation of Eomes expression.
背景
在 HIV 感染过程中，不同的机制驱动 CD4 和 CD8 T 细胞的免疫激活，导致 CD4 T 细胞耗竭和 CD8 T 细胞池的扩张。这种免疫激活是多克隆的，超出了 HIV 特异性 T 细胞的范围。这种免疫激活的一个后果是记忆 CD8 T 细胞上的白细胞介素 7 受体 α（CD127）表达显著下降。导致这种情况的机制尚不清楚，由于减少 IL-7 信号对 HIV 和其他病原体特异性记忆 T 细胞的潜在影响，在本研究中，我们研究了导致 CD127 下调的分子机制。
方法
通过 qRT-PCR 测定膜结合（mIL7RA）和可溶性（sIL7RA）mRNA 的表达。通过流式细胞术研究健康对照者和 HIV 感染者中 CD127、Eomesodermin（Eomes）和 T-bet 的表达。
结果
CD127 记忆 CD8 T 细胞中 mIL7RA 和 sIL7RA 剪接形式的 CD127 下调发生在转录水平。CD127 记忆 CD8 T 细胞表现出 Eomes 表达增加和“效应样”基因谱。这些变化与较高的 HIV-RNA 水平相关。在联合抗逆转录病毒治疗（cART）后，CD127 表达在较长时间（>5 个月）内增加，与 Eomes 表达降低相关。
结论
在与 Eomes 表达上调相关的情况下，记忆 CD8 T 细胞中 CD127 在转录水平下调。
Zotero 插件