Apoptosis of inflammatory cells in immune control of the nervous system: role of glia

Glia. 2001 Nov;36(2):137-44. doi: 10.1002/glia.1103.


The elimination of inflammatory cells within the central nervous system (CNS) by apoptosis plays an important role in protecting the CNS from immune-mediated damage. T cells, B cells, macrophages, and microglia all undergo apoptosis in the CNS. The apoptotic elimination of CNS-reactive T cells is particularly important, as these cells can recruit and activate other inflammatory cells. T-cell apoptosis contributes to the resolution of CNS inflammation and clinical recovery from attacks of experimental autoimmune encephalomyelitis (EAE), an animal model of the demyelinating disease multiple sclerosis (MS). T-cell apoptosis in the CNS in EAE occurs in both an antigen-specific and an antigen-nonspecific manner. In antigen-specific T-cell apoptosis, it is proposed that T cells that recognize their antigen in the CNS, such as CNS-reactive T cells, are deleted by the process of activation-induced apoptosis after activation of the T-cell receptor. This may result from the ligation of T-cell death receptors (such as CD95 (Fas) or tumor necrosis factor (TNF) receptor 1) by CD95 ligand (CD95L) or TNF expressed by the same T cell or possibly by microglia, astrocytes or neurons. Inadequate costimulation of the T cell by antigen-presenting glial cells may render T cells susceptible to activation-induced apoptosis. T cells expressing CD95 may also die in an antigen-nonspecific manner after interacting with glial cells expressing CD95L. Other mechanisms for antigen-nonspecific T-cell apoptosis include the endogenous release of glucocorticosteroids, deprivation of interleukin-2, and the release of nitric oxide by macrophages or glia. Apoptosis of autoreactive T cells in the CNS is likely to be important in preventing the development of autoimmune CNS diseases such as MS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Autoimmune Diseases of the Nervous System / immunology
  • Autoimmune Diseases of the Nervous System / metabolism
  • Autoimmune Diseases of the Nervous System / physiopathology
  • Central Nervous System / immunology*
  • Encephalitis / immunology*
  • Humans
  • Neuroglia / immunology*
  • Neuroglia / metabolism
  • Neurons / immunology
  • Neurons / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism