Apoptotic cells are present in the CNS throughout acute and chronic-progressive EAE in the absence of clinical recovery.
Experimental allergic encephalomyelitis (EAE) is an autoimmune, demyelinating disorder of the central nervous system induced in susceptible animals as a model for the human disease multiple sclerosis. Antibodies against the leukocyte adhesion molecule alpha4 integrin have been shown to prevent and reverse acute and chronic EAE of the guinea pig. The results presented in this paper implicate apoptosis as the mechanism of reversal of EAE following treatment with anti-alpha4 integrin antibody. Apoptotic cells were observed in the central nervous system (CNS) throughout chronic-progressive EAE of the guinea pig in the absence of clinical recovery. Many of the apoptotic cells were identified as T cells using immunohistochemistry. Similarly, apoptotic cells were present in the CNS of animals during anti-alpha4 integrin-mediated recovery from acute and chronic disease. Therefore, anti-alpha4 integrin-mediated recovery from EAE is due to the prevention of the influx of new inflammatory cells into the CNS that are required to replace those undergoing apoptosis.
Hyduk
S J
SJ
Department of Physiology, London Health Sciences Centre, University of Western Ontario, Canada.
Karlik
S J
SJ
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology; D002490:Central Nervous System / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006168:Guinea Pigs; D039441:Integrin alpha4; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D039441:Integrin alpha4