title: Minocycline modulates antigen-specific CTL activity through inactivation of mononuclear phagocytes in patients with HTLV-I associated neurologic disease.
abstract: BACKGROUND
  The activation of mononuclear phagocytes (MPs), including monocytes, macrophages and dendritic cells, contributes to central nervous system inflammation in various neurological diseases. In HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), MPs are reservoirs of HTLV-I, and induce proinflammatory cytokines and excess T cell responses. The virus-infected or activated MPs may play a role in immuneregulation and disease progression in patients with HTLV-I-associated neurological diseases.
  
  
  RESULTS
  Phenotypic analysis of CD14⁺ monocytes in HAM/TSP patients demonstrated high expression of CX3CR1 and HLA-DR in CD14lowCD16⁺ monocytes, compared to healthy normal donors (NDs) and asymptomatic carriers (ACs), and the production of TNF-α and IL-1β in cultured CD14⁺ cells of HAM/TSP patients. CD14⁺ cells of HAM/TSP patients also showed acceleration of HTLV-I Tax expression in CD4⁺ T cells. Minocycline, an inhibitor of activated MPs, decreased TNF-α expression in CD14⁺ cells and IL-1β release in PBMCs of HAM/TSP patients. Minocycline significantly inhibited spontaneous lymphoproliferation and degranulation/IFN-γ expression in CD8⁺ T cells of HAM/TSP patients. Treatment of minocycline also inhibited IFN-γ expression in CD8⁺ T cells of HAM/TSP patients after Tax11-19 stimulation and downregulated MHC class I expression in CD14⁺ cells.
  
  
  CONCLUSIONS
  These results demonstrate that minocycline directly inhibits the activated MPs and that the downregulation of MP function can modulate CD8⁺ T cells function in HAM/TSP patients. It is suggested that activated MPs may be a therapeutic target for clinical intervention in HAM/TSP.
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 USA.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Enose-Akahata
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Unsong
authors.initials: U
authors.lastname: Oh
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008911:Minocycline / Q000008:administration & dosage*; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy / Q000276:immunology*; D010586:Phagocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000956:Antigens, Viral; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D008911:Minocycline