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Journal of Neuroinflammation

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Open Access 01-12-2014 | Research

Chronic thoracic spinal cord injury impairs CD8⁺ T-cell function by up-regulating programmed cell death-1 expression

Authors: Ji Zha, Annalise Smith, Samita Andreansky, Valerie Bracchi-Ricard, John R Bethea

Published in: Journal of Neuroinflammation | Issue 1/2014

Abstract

Background

Chronic spinal cord injury (SCI) induces immune depression in patients, which contributes to their higher risk of developing infections. While defects in humoral immunity have been reported, complications in T-cell immunity during the chronic phase of SCI have not yet been explored.

Methods

To assess the impact of chronic SCI on peripheral T-cell number and function we used a mouse model of severe spinal cord contusion at thoracic level T9 and performed flow cytometry analysis on the spleen for T-cell markers along with intracellular cytokine staining. Furthermore we identified alterations in sympathetic activity in the spleen of chronic SCI mice by measuring splenic levels of tyrosine hydroxylase (TH) and norepinephrine (NE). To gain insight into the neurogenic mechanism leading to T-cell dysfunction we performed in vitro NE stimulation of T-cells followed by flow cytometry analysis for T-cell exhaustion marker.

Results

Chronic SCI impaired both CD4⁺ and CD8⁺ T-cell cytokine production. The observed T-cell dysfunction correlated with increased expression of programmed cell death 1 (PD-1) exhaustion marker on these cells. Blocking PD-1 signaling in vitro restored the CD8⁺ T-cell functional defect. In addition, we showed that chronic SCI mice had higher levels of splenic NE, which contributed to the T-cell exhaustion phenotype, as PD-1 expression on both CD4⁺ and CD8⁺ T-cells was up-regulated following sustained exposure to NE in vitro.

Conclusions

These studies indicate that alteration of sympathetic activity following chronic SCI induces CD8⁺ T-cell exhaustion, which in turn impairs T-cell function and contributes to immune depression. Inhibition of the exhaustion pathway should be considered as a new therapeutic strategy for chronic SCI-induced immune depression.

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Title: Chronic thoracic spinal cord injury impairs CD8+ T-cell function by up-regulating programmed cell death-1 expression
Authors: Ji Zha
Annalise Smith
Samita Andreansky
Valerie Bracchi-Ricard
John R Bethea
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2014
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-11-65

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Chronic thoracic spinal cord injury impairs CD8⁺ T-cell function by up-regulating programmed cell death-1 expression

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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