Logo image
Back
Chronic thoracic spinal cord injury impairs CD8+ T-cell function by up-regulating programmed cell death-1 expression
Journal article   Open access   Peer reviewed

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

Ji Zha, Annalise Smith, Samita Andreansky, Valerie Bracchi-Ricard and John R Bethea
Journal of neuroinflammation, v 11(1), pp 65-65
01 Apr 2014
DOI: https://doi.org/10.1186/1742-2094-11-65
PMID: 24690491
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1186/1742-2094-11-65View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals Apoptosis - drug effects Apoptosis - physiology Calcium Ionophores - pharmacology CD4-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - physiology Cell Proliferation - drug effects Cytokines - metabolism Disease Models, Animal Female Ionomycin - pharmacology Mice Mice, Inbred C57BL Norepinephrine - pharmacology Programmed Cell Death 1 Receptor - genetics Programmed Cell Death 1 Receptor - metabolism Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Tetradecanoylphorbol Acetate - pharmacology Tyrosine 3-Monooxygenase - metabolism Up-Regulation - drug effects Up-Regulation - physiology
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. 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. 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. 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.

Metrics

12 Record Views
49 citations in Web of Science
49 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
Neurosciences
Logo image