title: Dynamic acquisition of HTLV-1 tax protein by mononuclear phagocytes: Role in neurologic disease.
abstract: Pathology of HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP) is believed to be the result of "bystander damage" involving effector CD8 (+) T lymphocytes (CTLs) killing of virus infected cells. But the specific cellular events leading up to tissue injury are still unclear. Here, we developed the Microscopy Imaging of Cytotoxic T lymphocyte assay with Fluorescence emission (MI-CaFé), an optimized visualization analysis to explore the interactions between CTLs and virus infected or viral antigen presenting target cells. Various cell-to-cell formations can be observed and our results demonstrate elevated frequencies of CTL-target cell conjugates in HAM/TSP patient PBMCs compared to control PBMCs. Furthermore, HTLV-1 Tax protein expression can be localized at the cell-cell junctions and also tracked moving from an infected cell to a CD14 (+) mononuclear phagocyte (MP). Activation of CD14 (+) MPs in HAM/TSP patient PBMCs and antigenic presentation of HTLV-1 Tax by MPs can be inferred by their spontaneous cytotoxicity after 18h of in vitro culture. Given that CD4 (+) T lymphocytes are the primary reservoirs of HTLV-1 and MPs are scavenger cells responsible for pathogen clearance, spontaneous cytotoxicity against MPs in HAM/TSP PBMCs suggests a mechanism of chronic inflammation, secondary to low level of persistent virus infection within the central nervous system.
authors: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors: Eiji
authors: E
authors: Matsuura
authors: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Yoshimi
authors: Y
authors: Enose-Akahata
authors: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Karen
authors: K
authors: Yao
authors: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Unsong
authors: U
authors: Oh
authors: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
authors: Yuetsu
authors: Y
authors: Tanaka
authors: Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors: Hiroshi
authors: H
authors: Takashima
authors: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jacobsons@ninds.nih.gov.
authors: Steven
authors: S
authors: Jacobson
mesh_terms: D002478:Cells, Cultured; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009422:Nervous System Diseases / Q000276:immunology / Q000378:metabolism; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000378:metabolism*; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism*
keywords: CTL; HAM/TSP; HTLV-1; Tax