title: The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis.
abstract: The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)-specific T cells in Lewis rats, whereas transfer of S100beta- or myelin oligodendrocyte glycoprotein (MOG)-specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein(+) T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.
authors.affiliation: Department of Neuroimmunology, Max-Planck Institute for Neurobiology, 82152 Martinsried, Germany.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kawakami
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.forename: Thomas
authors.initials: T
authors.lastname: Ritter
authors.forename: Tjalf
authors.initials: T
authors.lastname: Ziemssen
authors.forename: Wolfgang E F
authors.initials: WE
authors.lastname: Klinkert
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Ellwart
authors.forename: Monika
authors.initials: M
authors.lastname: Bradl
authors.forename: Kimberly
authors.initials: K
authors.lastname: Krivacic
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
authors.forename: Christopher
authors.initials: C
authors.lastname: Linington
authors.forename: Alexander
authors.initials: A
authors.lastname: Flügel
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D002460:Cell Line; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology*; D049452:Green Fluorescent Proteins; D018836:Inflammation Mediators / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D009928:Organ Specificity; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D016207:Cytokines; D018836:Inflammation Mediators; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins