Coexpression of Fas/FasL and Bax on brain and infiltrating T cells in the central nervous system is closely associated with apoptotic cell death during autoimmune encephalomyelitis.
Recent studies have suggested that autoimmune inflammation elicited in the central nervous system (CNS) is subsided by apoptotic cell death of inflammatory cells. To elucidate the molecular mechanism of apoptosis of infiltrating T and other cells occurring in the CNS during autoimmune encephalomyelitis, we determined the type of apoptotic cells and the localization of apoptosis-related molecules (Fas, FasL, Bax, Bcl-2 and active caspase 3) by immunohistochemistry. Double labeling with the TUNEL method and cell-type markers showed that infiltrating T cells and microglia/macrophages underwent apoptosis, while astrocytes and neurons did not. Staining for apoptosis-related molecules revealed that infiltrating T cells and microglia/macrophages, but not astrocytes and neurons, expressed both Fas-FasL and Bax. The distribution and cell type of active caspase 3-positive cells were essentially the same as those of TUNEL-positive cells. These findings suggest that coexpression of Fas/FasL and Bax is closely associated with apoptotic cell death of infiltrating T cells and microglia in the CNS. Furthermore, astrocytes which express Fas and FasL, but not Bax, may play an important role in regulating inflammation in the CNS by inducing apoptotic cell death of infiltrating T cells and microglia, both of which have an inflammation-promoting nature.
Kohji
T
T
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6 Fuchu, Tokyo, Japan.
Matsumoto
Y
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D002465:Cell Movement; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology*; D014018:Tissue Distribution; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism*
C494828:Bax protein, rat; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor