title: The suppression of T cell apoptosis influences the severity of disease during the chronic phase but not the recovery from the acute phase of experimental autoimmune encephalomyelitis in mice.
abstract: The elimination of T cells by apoptosis is considered to be one of the regulatory factors in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To address further the role of apoptotic T cell death in EAE, we investigated myelin oligodendrocyte glycoprotein (MOG)-induced EAE in transgenic mice overexpressing the anti-apoptotic gene, bcl-2, in T cells. During the acute phase of EAE, no significant difference was observed in the clinical course, pathology and T cell response to MOG between bcl-2 transgenic mice and wild-type littermates. While the recovery from the first attack of EAE was not impaired in the bcl-2 transgenic mice, a more severe disease was observed during the chronic phase of the disease even though T and B cell responses to MOG were comparable to those of wild-type littermates. A flow cytometric analysis by Annexin V showed a significant decrease of apoptotic T cells in the central nervous system (CNS) of the bcl-2 transgenic mice with EAE compared with controls during the chronic as well as the acute phase of disease. These results suggest that while T cell apoptosis in the CNS may play a regulatory role in EAE, the spontaneous recovery from acute EAE cannot solely be explained by T cell apoptosis.
authors.affiliation: Neuroimmunology Laboratory, Department of Biochemistry, La Trobe University, Bundoora, Victoria 3083, Australia. yoshiok@bioserve.latrobe.edu.au
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okuda
authors.forename: Misa
authors.initials: M
authors.lastname: Okuda
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D019254:Genes, bcl-2; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009573:Nitrites / Q000032:analysis; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009573:Nitrites