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The Journal of Neuroscience, March 29, 2006, 26(13):3396-3403; doi:10.1523/JNEUROSCI.4767-05.2006

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Neurobiology of Disease
CD8+ Lymphocyte-Mediated Injury of Dorsal Root Ganglion Neurons during Lentivirus Infection: CD154-Dependent Cell Contact Neurotoxicity

Yu Zhu,¹ Joseph Antony,² Shuhong Liu,² Jose A. Martinez,² Fabrizio Giuliani,¹ Douglas Zochodne,² and Christopher Power^1,2

¹Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2, and ²Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada T2N 1N4

Correspondence should be addressed to Dr. Christopher Power, Department of Medicine, University of Alberta, 611 Heritage Medical Research Centre, Edmonton, Alberta, Canada T6G 2S2. Email: chris.power{at}ualberta.ca

Neuronal damage in dorsal root ganglia (DRGs) with accompanying axonal injury is a key feature of human immunodeficiency virus (HIV)-related distal sensory polyneuropathy (DSP). In a model of HIV-related DSP, we observed numerous CD3+ T lymphocytes (p < 0.05) in DRGs from feline immunodeficiency virus (FIV)-infected animals, which also exhibited low CD4+ and high CD8+ lymphocyte levels in blood accompanied by a selective loss of small-diameter sural nerve axons (p < 0.05). FIV-infected lymphocytes cocultured with syngeneic DRGs caused neuronal damage, indicated by neurite retraction, neuronal soma atrophy, and loss (p < 0.05). In contrast, supernatants from FIV-infected or uninfected lymphocytes were minimally neurotoxic, despite high FIV virion levels. Among lymphocyte subsets cocultured with DRG cultures, CD8+ T cells from both FIV-infected and uninfected lymphocytes selectively caused DRG neuronal injury (p < 0.05). FIV-infected CD8+ T cells showed markedly increased CD154 expression (p < 0.05), whereas neurons were the predominant cells expressing CD40 in DRGs. Blocking CD154 on activated CD8+ T cells protected DRG neurons (p < 0.05). These findings indicated that CD8+ T cells were principal effectors of DRG neuronal injury after FIV infection through a CD40–CD154 interaction in a cell contact-dependent manner.

Key words: dorsal root ganglia; HIV; FIV; CD154; neuron; lymphocyte

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Received Nov. 7, 2005; revised Dec. 28, 2005; accepted Jan. 14, 2006.

Correspondence should be addressed to Dr. Christopher Power, Department of Medicine, University of Alberta, 611 Heritage Medical Research Centre, Edmonton, Alberta, Canada T6G 2S2. Email: chris.power{at}ualberta.ca

This article has been cited by other articles:

				M. Sanchez-Ruiz, L. Wilden, W. Muller, W. Stenzel, A. Brunn, H. Miletic, D. Schluter, and M. Deckert Molecular Mimicry between Neurons and an Intracerebral Pathogen Induces a CD8 T Cell-Mediated Autoimmune Disease J. Immunol., June 15, 2008; 180(12): 8421 - 8433. [Abstract] [Full Text] [PDF]

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