CD4 + T Cells and Neuroprotection: Relevance to Motoneuron Injury and Disease

We have established a physiologically relevant mechanism of CD4+ T cell-mediated neuroprotection involving axotomized wildtype (WT) mouse facial motoneurons (FMN) with significance in the treatment of amyotrophic lateral sclerosis (ALS), a fatal MN disease. Use of the transgenic mouse model of ALS i...

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Bibliographic Details
Published in:Journal of neuroimmune pharmacology 2015-12, Vol.10 (4), p.587-594
Main Authors: Jones, Kathryn J., Lovett-Racke, Amy E., Walker, Chandler L., Sanders, Virginia M.
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - immunology
Animals
Biomedical and Life Sciences
Biomedicine
CD4-Positive T-Lymphocytes - immunology
Cell Biology
Humans
Immunology
Invited Review
Lymphocytes
Motor Neurons - immunology
Nerve Regeneration - immunology
Neuroprotection - immunology
Neurosciences
Pharmacology/Toxicology
Rodents
Virology
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Summary:We have established a physiologically relevant mechanism of CD4+ T cell-mediated neuroprotection involving axotomized wildtype (WT) mouse facial motoneurons (FMN) with significance in the treatment of amyotrophic lateral sclerosis (ALS), a fatal MN disease. Use of the transgenic mouse model of ALS involving expression of human mutant superoxide dismutase genes (SOD1 G93A ; abbreviated here as mSOD1) has accelerated basic ALS research. Superimposition of facial nerve axotomy (FNA) on the mSOD1 mouse during pre-symptomatic stages indicates that they behave like immunodeficient mice in terms of increased FMN loss and decreased functional recovery, through a mechanism that, paradoxically, is not inherent within the MN itself, but, instead, involves a defect in peripheral immune: CNS glial cell interactions. Our goal is to utilize our WT mouse model of immune-mediated neuroprotection after FNA as a template to elucidate how a malfunctioning peripheral immune system contributes to motoneuron cell loss in the mSOD1 mouse. This review will discuss potential immune defects in ALS, as well as provide an up-to-date understanding of how the CD4+ effector T cells provide neuroprotection to motoneurons through regulation of the central microglial and astrocytic response to injury. We will discuss an IL-10 cascade within the facial nucleus that requires a functional CD4+ T cell trigger for activation. The review will discuss the role of T cells in ALS, and our recent reconstitution experiments utilizing our model of T cell-mediated neuroprotection in WT vs mSOD1 mice after FNA. Identification of defects in neural:immune interactions could provide targets for therapeutic intervention in ALS.
ISSN:1557-1890
1557-1904
DOI:10.1007/s11481-015-9625-x