Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
Biomed Res Int. 2013;2013:796014. doi: 10.1155/2013/796014. Epub 2012 Dec 27.
Similar to HIV infection in humans, SIV infection in macaques induces progressive loss of immune cell components and function, resulting in immune deficiency in nearly all untreated infected subjects. In SIV-infected macaques, 25% of animals develop terminal AIDS within 6 months of infection. The factors responsible for the development of such rapid progression are unknown. We have previously found that defects in CD8+ T cells detectable from early infection correlate to rapid progression to simian AIDS. The transcriptional screening of molecular fingerprints on different steps along the activation/effector process of splenic CD8+ cells at termination revealed a distinction in rapid compared to regular progressors, which was characterized by a decrease in classic T cell receptor (TCR) components, and an increase in Toll-like receptor (TLR) and apoptotic pathways. A TLR pathway screening in lymphoid and myeloid cells from both the spleen and from the central nervous system of infected macaques revealed that the upregulation of TLR is not in the innate immune compartment, but rather in lymphoid cells that contain adaptive immune cells. Our findings suggest that opposing effects of TCR specific signaling and TLR engagement may drive the CD8 phenotypic failure that determines a rapid disease course in HIV infection.
类似于人类的 HIV 感染，SIV 感染猕猴会导致免疫细胞成分和功能逐渐丧失，导致几乎所有未经治疗的感染动物都出现免疫缺陷。在 SIV 感染的猕猴中，25%的动物在感染后 6 个月内发展为终末期 AIDS。导致这种快速进展的因素尚不清楚。我们之前发现，从早期感染即可检测到的 CD8+T 细胞缺陷与快速进展为猿猴 AIDS 相关。对终止时脾脏 CD8+细胞激活/效应过程不同步骤的分子指纹进行转录筛选，发现快速进展者与常规进展者之间存在差异，其特征是经典 T 细胞受体 (TCR) 成分减少，Toll 样受体 (TLR) 和凋亡途径增加。对感染猕猴的脾脏和中枢神经系统的淋巴样细胞和髓样细胞进行 TLR 途径筛选表明，TLR 的上调不是在固有免疫区，而是在包含适应性免疫细胞的淋巴样细胞中。我们的研究结果表明，TCR 特异性信号和 TLR 结合的相反作用可能导致 CD8 表型衰竭，从而决定 HIV 感染的快速病程。
