title: CD8 T cell-initiated blood-brain barrier disruption is independent of neutrophil support.
abstract: Blood-brain barrier (BBB) disruption is a common feature of numerous neurologic disorders. A fundamental question in these diseases is the extent inflammatory immune cells contribute to CNS vascular permeability. We have previously shown that CD8 T cells play a critical role in initiating BBB disruption in the peptide-induced fatal syndrome model developed by our laboratory. However, myelomonocytic cells such as neutrophils have also been implicated in promoting CNS vascular permeability and functional deficit in murine models of neuroinflammatory disease. For this reason, we evaluated neutrophil depletion in a murine model of CD8 T cell-initiated BBB disruption by employing traditionally used anti-granulocyte receptor-1 mAb RB6-8C5 and Ly-6G-specific mAb 1A8. We report that CNS-infiltrating antiviral CD8 T cells express high levels of granulocyte receptor-1 protein and are depleted by treatment with RB6-8C5. Mice treated with RB6-8C5, but not 1A8, display: 1) intact BBB tight junction proteins; 2) reduced CNS vascular permeability visible by gadolinium-enhanced T1-weighted magnetic resonance imaging; and 3) preservation of motor function. These studies demonstrate that traditional methods of neutrophil depletion with RB6-8C5 are broadly immune ablating. Our data also provide evidence that CD8 T cells initiate disruption of BBB tight junction proteins and CNS vascular permeability in the absence of neutrophil support.
authors: Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
authors: Holly L
authors: HL
authors: Johnson
authors: Yi
authors: Y
authors: Chen
authors: Fang
authors: F
authors: Jin
authors: Lisa M
authors: LM
authors: Hanson
authors: Jeffrey D
authors: JD
authors: Gamez
authors: Istvan
authors: I
authors: Pirko
authors: Aaron J
authors: AJ
authors: Johnson
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002199:Capillary Permeability / Q000276:immunology*; D018188:Cardiovirus Infections / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000276:immunology; D017945:Theilovirus