title: Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis.
abstract: i.v. infusion of native autoantigen or its altered peptide variants is an important therapeutic option for the treatment of autoimmune diseases, because it selectively targets the disease-inducing T cells. To learn more about the mechanisms and kinetics of this approach, we visualized the crucial initial effects of i.v. infusion of peptides or intact protein on GFP-tagged autoaggressive CD4(+) effector T cells using live-video and two-photon in situ imaging of spleens in living animals. We found that the time interval between i.v. injection of intact protein to first changes in T cell behavior was extremely short; within 10 min after protein application, the motility of the T cells changed drastically. They slowed down and became tethered to local sessile stromal cells. A part of the cells aggregated to form clusters. Within the following 20 min, IFN-gamma mRNA was massively (>100-fold) up-regulated; surface IL-2 receptor and OX-40 (CD 134) increased 1.5 h later. These processes depleted autoimmune T cells in the blood circulation, trapping the cells in the peripheral lymphoid organs and thus preventing them from invading the CNS. This specific blockage almost completely abrogated CNS inflammation and clinical disease. These findings highlight the speed and efficiency of antigen recognition in vivo and add to our understanding of T cell-mediated autoimmunity.
authors.affiliation: Max Planck Institute for Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.forename: Naoto
authors.initials: N
authors.lastname: Kawakami
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.forename: Chiara
authors.initials: C
authors.lastname: Cordiglieri
authors.forename: Kristina
authors.initials: K
authors.lastname: Streyl
authors.forename: Mikhail
authors.initials: M
authors.lastname: Nosov
authors.forename: Wolfgang E F
authors.initials: WE
authors.lastname: Klinkert
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Ellwart
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
authors.forename: Alexander
authors.initials: A
authors.lastname: Flügel
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D002465:Cell Movement; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005786:Gene Expression Regulation; D007167:Immunotherapy; D007275:Injections, Intravenous; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D051381:Rats; D012995:Solubility; D013154:Spleen / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D001324:Autoantigens; D004676:Myelin Basic Protein