Bystander killing of neurons by cytotoxic T cells specific for a glial antigen

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


To explore pathways to neuron loss in inflammatory diseases, transgenic mice expressing β-galactosidase (β-gal) in either astrocytes or photoreceptor cells, or both, were inoculated with activated, β-gal-specific cytotoxic CD8 T lymphocytes (CTLs). β-gal-positive astrocytes in brain were rapidly attacked, with particular damage in cerebellum. Substantial loss of cerebellar granule cells was found, even though these neurons did not express β-gal. The small number of β-gal-positive retinal astrocytes present in these mice was also rapidly destroyed by transferred CTLs, but without detectable consequences for retinal neurons. However, in mice with photoreceptor cell-specific β-gal expression, near-total destruction of photoreceptor cells was produced by CTL transfer. Attack on photoreceptor cells displayed minimal inflammation, and onset was a week later than onset of astrocyte-directed disease. CTL transfer into F 1 mice expressing β-gal in both astrocytes and photoreceptor cells confirmed that pathogenesis directed against antigen expressed in glia versus neurons proceeded in two distinct, independent phases, β-gal-positive retinal astrocytes were severely affected by 5 days post-transfer, followed by rapid resolution. Photoreceptor cells in the same retina were unaffected until 12 days post-transfer. The susceptibility of photoreceptor cells was not enhanced by the prior CTL attack on β-gal-expressing retinal astrocytes. The results demonstrate that extensive bystander killing of neurons can occur in vivo as a result of direct CTL attack on surrounding astrocytes. Antigen-expressing retinal neurons were also efficiently killed by CTLs, but by a mechanism that was substantially delayed and dissociated from the killing of retinal astrocytes.

Original languageEnglish (US)
Pages (from-to)457-466
Number of pages10
Issue number5
StatePublished - Apr 1 2006


  • Antigen-presenting cells
  • Autoimmunity
  • CD8 T cells
  • Immunopathogenesis
  • Neuroimmunology


Dive into the research topics of 'Bystander killing of neurons by cytotoxic T cells specific for a glial antigen'. Together they form a unique fingerprint.

Cite this