title: HTLV-1 induces a Th1-like state in CD4+CCR4+T cells that produces an inflammatory positive feedback loop via astrocytes in HAM/TSP.
abstract: The main feature of Human T-lymphotropic virus type I (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis is a virus-induced hyperactive immune response that produces chronic inflammation in the central nervous system (CNS), but the mechanism by which HTLV-1 deregulates the immune response is unknown. We recently reported a high frequency of HTLV-1-infected CCR4+cells, including regulatory T cells. We showed that HTLV-1 induces a Th1-like state in these CCR4+cells via T-bet expression. We have also found that CXCL10 plays an important role in a positive feedback loop that maintains inflammation in the CNS. Astrocytes, which were found to be the main producers of CXCL10 in the CNS, are another key player in the loop. In short, we postulate that infected CCR4+Th1-like T cells produce interferon-γ, which stimulates astrocytes to produce CXCL10. We now have a much better understanding of the molecular mechanisms at play in HAM/TSP pathogenesis.
authors.affiliation: Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan. Electronic address: yyamano@marianna-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamano
authors.affiliation: Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Ariella
authors.initials: A
authors.lastname: Coler-Reilly
mesh_terms: D001253:Astrocytes / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods; D025461:Feedback, Physiological / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000378:metabolism*; D054398:Receptors, CCR4 / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: C515354:CCR4 protein, human; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D054398:Receptors, CCR4
keywords: Astrocyte; CCR4; CXCL10; CXCR3; HAM; HTLV-1