title: CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke.
abstract: While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke.
authors.affiliation: Department of Neurology, University Clinics Würzburg, Würzburg, Germany.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schuhmann
authors.affiliation: 1] Department of Neurology, University Clinics Würzburg, Würzburg, Germany [2] Institute of Clinical Epidemiology and Biometry, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Neurology, University Clinics Würzburg, Würzburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lorenz
authors.affiliation: 1] Department of Neurology, University of Münster, Münster, Germany [2] Institute of Physiology I-Neuropathophysiology, University of Münster, Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Beyersdorf
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerkau
authors.affiliation: Department of Neurology, University Clinics Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D018106:CD28 Antigens / Q000819:agonists* / Q000276:immunology; D002560:Cerebrovascular Circulation / Q000276:immunology; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000276:immunology / Q000473:pathology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013927:Thrombosis / Q000097:blood / Q000276:immunology / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D018398:Homeodomain Proteins; C064658:RAG-1 protein