T cells contribute to lysophosphatidylcholine-induced macrophage activation and demyelination in the CNS

Nader Ghasemlou, Young Jeong Suh, Steve Lacroix, Samuel David

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

We have previously shown that intraspinal microinjection of lysophosphatidylcholine (LPC), a potent demyelinating agent, results in a rapid but brief influx of T cells (between 6 and 12 h). This is accompanied by a robust activation of macrophages/microglia that leads to demyelination by 48 h. In the present study, we examined whether this brief influx of T cells contributes to the activation of macrophages/microglia and demyelination by injecting LPC into the dorsal column white matter of athymic Nude mice that lack T cells. We show that there is a significant reduction in macrophage/ microglial activation and myelin clearance after LPC injection in Nude mice as compared with wildtype controls. We also show that there is no difference in the recruitment of hematogenous macrophages into the spinal cord after LPC injection in the two mouse strains. Of the T cell cytokines assessed, there was a marked reduction in the mRNA expression of interleukin-2 (IL-2) in Nude mice compared with wildtype animals. Neutralizing IL-2 with function-blocking antibodies in wildtype animals resulted in a significant decrease in the number of phagocytic macrophages/microglia and a reduction in demyelination induced by LPC. While there may be other defects in Nude mice that might contribute to the effects shown here, these data suggest that the brief influx of T cells in this model of chemically-induced demyelination could play a role in macrophage/microglial activation and demyelination. These results may also have implications for remyelination in this and other types of CNS damage.

Original languageEnglish (US)
Pages (from-to)294-302
Number of pages9
JournalGLIA
Volume55
Issue number3
DOIs
StatePublished - Feb 2007
Externally publishedYes

Keywords

  • CNS inflammation
  • Cytokines
  • Macrophages
  • Myelin
  • Spinal cord

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'T cells contribute to lysophosphatidylcholine-induced macrophage activation and demyelination in the CNS'. Together they form a unique fingerprint.

Cite this