Effective and selective immune surveillance of the brain by MHC class I-restricted cytotoxic T lymphocytes

Eur J Immunol. 2003 May;33(5):1174-82. doi: 10.1002/eji.200323492.


Cytotoxic CD8(+) T cells are abundantly present in human virus-induced or putative autoimmune diseases of the central nervous system (CNS). Their direct role in the induction of inflammatory brain damage is, however, poorly understood. We have studied CD8(+) T cell-mediated brain inflammation by transferring MHC class I-restricted hemagglutinin (HA)-reactive T cells from a TCR transgenic mouse line into transgenic mice, which express HA in astrocytes. We show that activated CD8(+) T cells alone can induce monophasic brain inflammation in immunocompetent recipient animals. Similar to previous studies, involving transfer of CD4(+) cells, brain inflammation peaks after 5-7 days and then declines. The pathology of brain inflammation, however, differs fundamentally from that induced by CD4(+) cells. The inflammatory reaction is dominated by T cells and activated microglia in the virtual absence of hematogenous macrophages. This is associated with exquisitely specific destruction of antigen-containing astrocytes in the absence of any bystander damage of myelin, oligodendrocytes or neurons. Furthermore, in contrast to CD4(+) T cells, some CD8(+) cells accumulate in the brain and activate microglia in recipient animals, even in the absence of the specific antigen in the CNS. These data indicate that CD8(+) T cells are prime candidates for immune surveillance of the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology*
  • Brain / pathology
  • Encephalitis / etiology
  • Encephalitis / immunology
  • Encephalitis / pathology
  • Glial Fibrillary Acidic Protein / analysis
  • Histocompatibility Antigens Class I / physiology*
  • Macrophages / physiology
  • Mice
  • Mice, Transgenic
  • Microglia / physiology
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / analysis
  • T-Lymphocytes, Cytotoxic / immunology*


  • Glial Fibrillary Acidic Protein
  • Histocompatibility Antigens Class I
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins