Apoptosis of inflammatory cells in immune control of the nervous system: role of glia.
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.
Pender
M P
MP
Department of Medicine, University of Queensland, Brisbane, Australia.
Rist
M J
MJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002490:Central Nervous System / Q000276:immunology*; D004660:Encephalitis / Q000276:immunology*; D006801:Humans; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism