On the pathogenic role of brain-sequestered alphabeta CD8+ T cells in experimental cerebral malaria.
Cerebral malaria (CM) develops in a small proportion of persons infected with Plasmodium falciparum and accounts for a substantial proportion of the mortality due to this parasite. The actual pathogenic mechanisms are still poorly understood, and in humans investigations of experimental CM are unethical. Using an established Plasmodium berghei-mouse CM model, we have investigated the role of host immune cells at the pathological site, the brain. We report in this study the detailed quantification and characterization of cells, which migrated and sequestered to the brain of mice with CM. We demonstrated that CD8(+) alphabeta T cells, which sequester in the brain at the time when neurological symptoms appear, were responsible for CM mortality. These observations suggest a mechanism which unifies disparate observations in humans.
Belnoue
Elodie
E
Département d'Immunologie, Institut Cochin, Institut National de la Santé et de la Recherche Médicale Unité 567, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Hôpital Cochin, Université René Descartes, Paris, France.
Kayibanda
Michèle
M
Vigario
Ana M
AM
Deschemin
Jean-Christophe
JC
van Rooijen
Nico
N
Viguier
Mireille
M
Snounou
Georges
G
Rénia
Laurent
L
D000818:Animals; D001921:Brain / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D016779:Malaria, Cerebral / Q000209:etiology* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000209:etiology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta