title: A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity.
abstract: Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluorescently labeled nuclear factor of activated T cells (NFAT) with histone protein H2B to create a broadly applicable molecular sensor for intravital imaging of T cell activation. In experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, we report that effector T cells entering the CNS become activated after short contacts with leptomeningeal phagocytes. During established disease, the activation process is extended to the depth of the CNS parenchyma, where the cells form contacts with microglia and recruited phagocytes. We show that it is the activation processes during the preclinical phase rather than during established disease that are essential for the intensity and duration of the disease bout.
authors.affiliation: Institute for Multiple Sclerosis Research and Department of Neuroimmunology, Gemeinnützige Hertie-Stiftung and University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Lodygin
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.forename: Christian
authors.initials: C
authors.lastname: Schläger
authors.forename: Henrike
authors.initials: H
authors.lastname: Körner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kitz
authors.forename: Michail
authors.initials: M
authors.lastname: Nosov
authors.forename: Jens
authors.initials: J
authors.lastname: van den Brandt
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Michael
authors.initials: M
authors.lastname: Haberl
authors.forename: Alexander
authors.initials: A
authors.lastname: Flügel
mesh_terms: D000818:Animals; D015551:Autoimmunity; D015374:Biosensing Techniques; D001921:Brain / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005453:Fluorescence; D006657:Histones / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006657:Histones; D050778:NFATC Transcription Factors