CD8+ lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain

J Med Primatol. 2011 Oct;40(5):300-9. doi: 10.1111/j.1600-0684.2011.00475.x. Epub 2011 Apr 4.

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 ((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.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Astrocytes / virology
  • Brain / metabolism
  • Brain / pathology*
  • Brain / virology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / virology
  • Disease Models, Animal
  • Encephalitis, Viral / immunology
  • Encephalitis, Viral / metabolism
  • Encephalitis, Viral / pathology
  • Encephalitis, Viral / veterinary
  • Flow Cytometry / veterinary
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry / veterinary
  • Lymphocyte Depletion / veterinary*
  • Macaca mulatta*
  • Magnetic Resonance Spectroscopy
  • Microfilament Proteins / metabolism
  • Microglia / metabolism
  • Microglia / pathology
  • Microglia / virology
  • Microtubule-Associated Proteins / metabolism
  • Monkey Diseases / immunology
  • Monkey Diseases / pathology
  • Monkey Diseases / virology
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / virology
  • Protons
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / pathology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / physiology
  • Synaptophysin / metabolism

Substances

  • Antibodies, Monoclonal
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Protons
  • Synaptophysin