title: Non-invasive tracking of CD4+ T cells with a paramagnetic and fluorescent nanoparticle in brain ischemia.
abstract: Recent studies have demonstrated that lymphocytes play a key role in ischemic brain injury. However, there is still a lack of viable approaches to non-invasively track infiltrating lymphocytes and reveal their key spatiotemporal events in the inflamed central nervous system (CNS). Here we describe an in vivo imaging approach for sequential monitoring of brain-infiltrating CD4(+) T cells in experimental ischemic stroke. We show that magnetic resonance imaging (MRI) or Xenogen imaging combined with labeling of SPIO-Molday ION Rhodamine-B (MIRB) can be used to monitor the dynamics of CD4(+) T cells in a passive transfer model. MIRB-labeled CD4(+) T cells can be longitudinally visualized in the mouse brain and peripheral organs such as the spleen and liver after cerebral ischemia. Immunostaining of tissue sections showed similar kinetics of MIRB-labeled CD4(+) T cells when compared with in vivo observations. Our results demonstrated the use of MIRB coupled with in vivo imaging as a valid method to track CD4(+) T cells in ischemic brain injury. This approach will facilitate future investigations to identify the dynamics and key spatiotemporal events for brain-infiltrating lymphocytes in CNS inflammatory diseases.
authors.affiliation: Departments of Neurology, Immunology, Radiology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Jin
authors.affiliation: Departments of Neurology, Immunology, Radiology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Departments of Neurology, Immunology, Radiology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Minshu
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Samuel Xiang-Yu
authors.initials: SX
authors.lastname: Shi
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Wood
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA qliu@tijmu.edu.cn.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Departments of Neurology, Immunology, Radiology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Departments of Neurology, Immunology, Radiology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Departments of Neurology, Immunology, Radiology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.affiliation: Departments of Neurology, Immunology, Radiology, Key Laboratory of Neurorepair and Regeneration, Tianjin and Ministry of Education, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000097:blood* / Q000000981:diagnostic imaging / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D058948:Cell Tracking / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012235:Rhodamines / Q000737:chemistry; D013194:Staining and Labeling / Q000379:methods
chemical_list: D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; C499308:Rag2 protein, mouse; D012235:Rhodamines; C029773:rhodamine B
keywords: CD4+ T cells; In vivo imaging; Ischemic stroke; USPIO; lymphocytes