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Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury

S D'Souza, K Alinauskas, E McCrea, C Goodyer and JP Antel
Journal of Neuroscience 1 November 1995, 15 (11) 7293-7300; DOI: https://doi.org/10.1523/JNEUROSCI.15-11-07293.1995
S D'Souza
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
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K Alinauskas
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
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E McCrea
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
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C Goodyer
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
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JP Antel
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
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Abstract

We examined whether oligodendrocytes, neurons, and astroglia derived from the human central nervous system differ in susceptibility to injury mediated by tumor necrosis factor (TNF)-alpha and by activated CD4+ T cells acting via a TNF-independent mechanism. Injury was assessed either as cell membrane-directed (lysis), measured by 51chromium (Cr) or lactate dehydrogenase (LDH) release, or nucleus- directed (apoptosis), measured by morphologic features based on propidium iodide (PI) staining and by DNA fragmentation measured by a terminal transferase (TdT)-mediated dUTP biotin nick end labeling technique (TUNEL). TNF did not induce 51Cr or LDH release in any cell targets, but did induce nuclear (66 +/- 2% of cells) and DNA (68 +/- 2% of cells) fragmentation selectively in the oligodendrocytes over 96 hr. At this time, there was no significant loss of oligodendrocyte cell number. Nuclear injury could be induced in neurons by serum deprivation and in malignant astrocytes by the combination of TNF and low serum. CD4+ T cells activated with phytohemagglutin (pha) or anti-CD3 plus interleukin-2 induced significant 51Cr and LDH release in all target cells tested; only pha-activated CD4+ T-cell cocultures showed reduced target cell numbers. Significant nuclear fragmentation was observed only for glioma cells (22 +/- 1% of cells). Differences in susceptibility to different immune effector mechanisms and in the nature of the injury response to the same effector mediator among human CNS-derived neural cells will need to be considered in design of therapeutic strategies aimed at protecting or limiting target cell injury consequent to disease or trauma.

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The Journal of Neuroscience: 15 (11)
Journal of Neuroscience
Vol. 15, Issue 11
1 Nov 1995
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Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury
S D'Souza, K Alinauskas, E McCrea, C Goodyer, JP Antel
Journal of Neuroscience 1 November 1995, 15 (11) 7293-7300; DOI: 10.1523/JNEUROSCI.15-11-07293.1995

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Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury
S D'Souza, K Alinauskas, E McCrea, C Goodyer, JP Antel
Journal of Neuroscience 1 November 1995, 15 (11) 7293-7300; DOI: 10.1523/JNEUROSCI.15-11-07293.1995
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