Longitudinal in vivo positron emission tomography imaging of infected and activated brain macrophages in a macaque model of human immunodeficiency virus encephalitis correlates with central and peripheral markers of encephalitis and areas of synaptic degeneration
Longitudinal in vivo positron emission tomography imaging of infected and activated brain macrophages in a macaque model of human immunodeficiency virus encephalitis correlates with central and peripheral markers of encephalitis and areas of synaptic degeneration
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DOI：
10.2353/ajpath.2008.070967
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发表时间：
2008-06-01
影响因子：
6
通讯作者：
Wiley, Clayton A.
中科院分区：
文献类型：
--
作者：
Venneti, Sriram;Bonneh-Barkay, Dafna;Wiley, Clayton A.
人类免疫缺陷病毒性脑炎的特征是感染和活化的巨噬细胞浸润大脑;然而，尚不清楚为什么25%的免疫抑制型获得性免疫缺陷综合征患者在感染不同长度后会发生疾病。我们确定在体内相关的（外周血和中枢神经系统）的发展和进展的慢病毒性脑炎的纵向以下感染和激活的巨噬细胞;在大脑中使用正电子发射断层扫描（PET）。使用来自慢病毒感染的脑炎患者和细胞培养系统的人死后脑组织，我们表明PET配体[H-3]（R）-PK 11195特异性结合病毒感染和活化的巨噬细胞。我们使用[C-11]（R）-PK 11195对一组感染猴免疫缺陷病毒的猕猴中感染和活化的脑巨噬细胞进行纵向成像。[C-11]（R）-PK 11195在脑中的体内滞留与脑和脑脊液中的病毒负荷以及突触前和突触后损伤区域相关。最后，[C-11]（R）-PK 11195在体内脑内滞留的纵向变化与外周血循环单核细胞以及自然杀伤和记忆CD 4（+）T细胞的变化相关。我们的研究结果表明，猴免疫缺陷病毒脑炎在体内的发生和发展与外周特定细胞亚型的变化相关。PET成像和这些外周免疫参数评估的结合可能有助于对活体患者慢病毒脑炎的纵向评估以及治疗效果的评估。
Human immunodeficiency virus encephalitis is characterized by infiltration of the brain with infected and activated macrophages; however, it is not known why disease occurs after variable lengths of infection in 25% of immunosuppressed acquired immune deficiency syndrome patients. We determined in vivo correlates (in peripheral blood and the central nervous system) for the development and progression of lentiviral encephalitis by longitudinally following infected and activated macrophages; in the brain using positron emission tomography (PET). Using human postmortem brain tissues from both lentivirus-infected encephalitic patients and cell culture systems, we showed that the PET ligand [H-3](R)-PK11195 bound specifically to virus-infected and activated macrophages. We longitudinally imaged infected and activated brain macrophages in a cohort of macaques infected with simian immunodeficiency virus using [C-11](R)-PK11195. [C-11](R)-PK11195 retention in vivo in the brain correlated with viral burden in the brain and cerebrospinal fluid, and with regions of both presynaptic and postsynaptic damage. Finally, longitudinal changes in [C-11](R)-PK11195 retention in the brain in vivo correlated with changes in circulating monocytes as well as in both natural killer and memory CD4(+) T cells in the periphery. our results suggest that development and progression of simian immunodeficiency virus encephalitis in vivo correlates with changes in specific cell subtypes in the periphery. A combination of PET imaging and the assessment of these peripheral immune parameters may facilitate longitudinal assessment of lentiviral encephalitis in living patients as well as evaluation of therapeutic efficacies.