Oligodendrocyte susceptibility to injury by T-cell perforin.
Myelin injury in multiple sclerosis (MS) appears to be immune mediated, but the mechanisms remain unidentified. It has been shown previously that oligodendrocytes, which synthesize and maintain myelin in the central nervous system (CNS), are susceptible to attack by homologous complement and that injury may be reversible when lysis is resisted by vesicular removal of membrane attack complexes. Here it is reported that oligodendrocytes are also highly susceptible to attack by T-cell perforin, and respond similarly to sublethal attack by shedding membrane vesicles. These findings imply that oligodendrocytes are vulnerable to lysis and/or reversible injury by a variety of closely related pore-forming immune effectors; following blood-brain barrier disruption, attack by one or several of these molecules may cause transient or irreversible myelin injury. Furthermore, these results provide the first indication that vesicular repair mechanisms may allow nucleated cells to recover from perforin-mediated cell injury.
Scolding
N J
NJ
Department of Neurology, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital.
Jones
J
J
Compston
D A
DA
Morgan
B P
BP
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000494:pharmacology*; D008854:Microscopy, Electron; D009836:Oligodendroglia / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011419:Propidium / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D011419:Propidium