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

Kathryn J. Jones, Amy E. Lovett-Racke, Chandler L. Walker, Virginia M. Sanders

Research output: Contribution to journalReview article

7 Scopus citations

Abstract

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 (SOD1G93A; 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.

Original languageEnglish (US)
Pages (from-to)587-594
Number of pages8
JournalJournal of Neuroimmune Pharmacology
Volume10
Issue number4
DOIs
StatePublished - Dec 1 2015

Keywords

  • ALS
  • Motoneurons
  • Neuroprotection
  • Neuroregeneration
  • T cells

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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