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CD8+ lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain
Authors: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
Institution:Neuroradiology Division and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
Abstract:Background 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. Methods Four rhesus macaques were monitored by proton magnetic resonance spectroscopy (1H‐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. Results CD8‐depleted animals showed stable metabolite levels and revealed no neuronal injury, astrogliosis or microglial activation in contrast to SIV‐infected animals. Conclusions 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.
Keywords:accelerated SIV macaque model  Magnetic resonance spectroscopy  NeuroAIDS
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