title: 2-photon imaging of phagocyte-mediated T cell activation in the CNS.
abstract: Autoreactive T cells can infiltrate the CNS to cause disorders such as multiple sclerosis. In order to visualize T cell activation in the CNS, we introduced a truncated fluorescent derivative of nuclear factor of activated T cells (NFAT) as a real-time T cell activation indicator. In experimental autoimmune encephalomyelitis, a rat model of multiple sclerosis, we tracked T cells interacting with structures of the vascular blood-brain barrier (BBB). 2-photon imaging documented the cytoplasmic-nuclear translocation of fluorescent NFAT, indicative of calcium-dependent activation of the T cells in the perivascular space, but not within the vascular lumen. The activation was related to contacts with the local antigen-presenting phagocytes and was noted only in T cells with a high pathogenic potential. T cell activation implied the presentation of an autoantigen, as the weakly pathogenic T cells, which remained silent in the untreated hosts, were activated upon instillation of exogenous autoantigen. Activation did not cogently signal long-lasting arrest, as individual T cells were able to sequentially contact fresh APCs. We propose that the presentation of local autoantigen by BBB-associated APCs provides stimuli that guide autoimmune T cells to the CNS destination, enabling them to attack the target tissue.
authors: Max Planck Institute of Neurobiology, Department of Neuroimmunology, Martinsried, Germany.
authors: Marija
authors: M
authors: Pesic
authors: Ingo
authors: I
authors: Bartholomäus
authors: Nikolaos I
authors: NI
authors: Kyratsous
authors: Vigo
authors: V
authors: Heissmeyer
authors: Hartmut
authors: H
authors: Wekerle
authors: Naoto
authors: N
authors: Kawakami
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001812:Blood-Brain Barrier / Q000473:pathology; D002450:Cell Communication; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D058948:Cell Tracking / Q000379:methods; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D008578:Meninges / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D018715:Microscopy, Video; D050778:NFATC Transcription Factors / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D050778:NFATC Transcription Factors; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins