Ratai E-M, Pilkenton S, He J, Fell R, Bombardier J P, Joo C-G, Lentz M R, Kim W-K, Burdo T H, Autissier P, Annamalai L, Curran E, O'Neil S P, Westmoreland S V, Williams K C, Masliah E, Gilberto González R
Neuroradiology Division and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
J Med Primatol. 2011 Oct;40(5):300-9. doi: 10.1111/j.1600-0684.2011.00475.x. Epub 2011 Apr 4.
Simian immunodeficiency virus (SIV) infection and persistent CD8(+) lymphocyte depletion rapidly leads to encephalitis and neuronal injury. The objective of this study is to confirm that CD8 depletion alone does not induce brain lesions in the absence of SIV infection.
Four rhesus macaques were monitored by proton magnetic resonance spectroscopy ((1) H-MRS) before and biweekly after anti-CD8 antibody treatment for 8 weeks and compared with four SIV-infected animals. Post-mortem immunohistochemistry was performed on these eight animals and compared with six uninfected, non-CD8-depleted controls.
CD8-depleted animals showed stable metabolite levels and revealed no neuronal injury, astrogliosis or microglial activation in contrast to SIV-infected animals.
Alterations observed in MRS and lesions in this accelerated model of neuroAIDS result from unrestricted viral expansion in the setting of immunodeficiency rather than from CD8(+) lymphocyte depletion alone.
猿猴免疫缺陷病毒(SIV)感染及持续性CD8(+)淋巴细胞耗竭会迅速导致脑炎和神经元损伤。本研究的目的是确认在没有SIV感染的情况下,单纯的CD8细胞耗竭不会诱发脑损伤。
对4只恒河猴在抗CD8抗体治疗前及治疗8周期间每两周进行一次质子磁共振波谱((1)H-MRS)监测,并与4只感染SIV的动物进行比较。对这8只动物进行死后免疫组化分析,并与6只未感染、未进行CD8细胞耗竭的对照动物进行比较。
与感染SIV的动物相比,CD8细胞耗竭的动物代谢物水平稳定,未出现神经元损伤、星形胶质细胞增生或小胶质细胞激活。
在这种加速的神经艾滋病模型中,磁共振波谱观察到的变化及病变是由免疫缺陷情况下不受限制的病毒扩增引起的,而非单纯由CD8(+)淋巴细胞耗竭导致。