Apoptosis of infiltrating T cells in the central nervous system of mice infected with Theiler's murine encephalomyelitis virus.
Theiler murine encephalomyelitis virus (TMEV), DA strain, induces in susceptible strain of mice a biphasic disease consisting of early acute disease followed by late chronic demyelinating disease. Both phases of the disease are associated with inflammatory infiltrates of the central nervous system (CNS). Late chronic demyelinating disease induced by TMEV serves as an excellent model to study human demyelinating disease, multiple sclerosis. During early acute disease, the virus is partially cleared from the CNS by CD3(+) T cells. These T cells express Fas, FasL, negligible levels of Bcl-2 proteins and undergo activation-induced cell death as determined by TUNEL assay leading to resolution of the inflammatory response. In contrast, during late chronic demyelinating disease, and despite dense perivascular and leptomeningeal infiltrates, only very few cells undergo apoptosis. Mononuclear cells infiltrating the CNS express Bcl-2. It appears that the lack of apoptosis of T cells during late chronic demyelinating disease leads to the accumulation of these cells in the CNS. These cells may play a role in the pathogenesis of the demyelinating disease.
Department of Anatomy and Cell Biology, and Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA. eoleszak@astro.temple.edu
Emilia L
EL
Oleszak
Brad E
BE
Hoffman
J Robert
JR
Chang
Ewa
E
Zaczynska
John
J
Gaughan
Christos D
CD
Katsetos
Chris D
CD
Platsoucas
Nile
N
Harvey
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism*; D018188:Cardiovirus Infections / Q000276:immunology / Q000821:virology; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D002908:Chronic Disease; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D017945:Theilovirus / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor