title: Brain dendritic cells in ischemic stroke: time course, activation state, and origin.
abstract: The immune response to stroke is comprised of inflammatory and regulatory processes. One cell type involved in both innate and adaptive immunity is the dendritic cell (DC). A DC population residing in the healthy brain (bDC) was identified using a transgenic mouse expressing enhanced yellow fluorescent protein (EYFP) under the promoter for the DC marker, CD11c (CD11c/EYFP Tg). To determine if bDC are involved in the immune response to cerebral ischemia, transient (40 min) middle cerebral artery occlusion (MCAO) followed by 6, 24, or 72 h reperfusion was conducted in CD11c/EYFP Tg mice. Our results demonstrated that DC accumulated in the ischemic hemisphere at 24 h post-MCAO-reperfusion, particularly in the border region of the infarct where T lymphocytes accrued. To distinguish resident bDC from the infiltrating peripheral DC, radiation chimeras [1. wild type (WT) hosts restored with CD11c/EYFP Tg bone marrow (BM) or 2. CD11c/EYFP Tg hosts restored with WT BM] were generated and examined by immunocytochemistry. These data confirmed that DC populating the core of the infarct at 72 h were of peripheral origin, whereas those in the border region were comprised primarily of resident bDC. The brain resident (CD45 intermediate) cells of CD11c/EYFP Tg mice were analyzed by flow cytometry. Compared to microglia, bDC displayed increased major histocompatibility class II (MHC II) and co-stimulatory molecules following MCAO-reperfusion. High levels of MHC II and the co-stimulatory molecule CD80 on bDC at 72 h corresponded to peak lymphocyte infiltration, and suggested a functional interaction between these two immune cell populations.
authors.affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Felger
authors.forename: Takato
authors.initials: T
authors.lastname: Abe
authors.forename: Ulrike W
authors.initials: UW
authors.lastname: Kaunzner
authors.forename: Andres
authors.initials: A
authors.lastname: Gottfried-Blackmore
authors.forename: Judit
authors.initials: J
authors.lastname: Gal-Toth
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
authors.forename: Karen
authors.initials: K
authors.lastname: Bulloch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000276:immunology*; D002545:Brain Ischemia / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000276:immunology; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology; D020521:Stroke / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D039521:CD11c Antigen