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

✍ Scribed by Michael P. Pender; Michael J. Rist

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 79 KB
• Volume: 36
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.1103

✦ Synopsis

Abstract

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. GLIA 36:137–144, 2001. © 2001 Wiley‐Liss, Inc.