[Updated on July 12] Integration of CiNii Articles into CiNii Research from April 1, 2022

Minocycline modulates antigen-specific CTL activity through inactivation of mononuclear phagocytes in patients with HTLV-I associated neurologic disease

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Phenotypic analysis of CD14<jats:sup>+</jats:sup> monocytes in HAM/TSP patients demonstrated high expression of CX<jats:sub>3</jats:sub>CR1 and HLA-DR in CD14<jats:sup>low</jats:sup>CD16<jats:sup>+</jats:sup> monocytes, compared to healthy normal donors (NDs) and asymptomatic carriers (ACs), and the production of TNF-α and IL-1β in cultured CD14<jats:sup>+</jats:sup> cells of HAM/TSP patients. CD14<jats:sup>+</jats:sup> cells of HAM/TSP patients also showed acceleration of HTLV-I Tax expression in CD4<jats:sup>+</jats:sup> T cells. Minocycline, an inhibitor of activated MPs, decreased TNF-α expression in CD14<jats:sup>+</jats:sup> cells and IL-1β release in PBMCs of HAM/TSP patients. Minocycline significantly inhibited spontaneous lymphoproliferation and degranulation/IFN-γ expression in CD8<jats:sup>+</jats:sup> T cells of HAM/TSP patients. Treatment of minocycline also inhibited IFN-γ expression in CD8<jats:sup>+</jats:sup> T cells of HAM/TSP patients after Tax11-19 stimulation and downregulated MHC class I expression in CD14<jats:sup>+</jats:sup> cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>These results demonstrate that minocycline directly inhibits the activated MPs and that the downregulation of MP function can modulate CD8<jats:sup>+</jats:sup> T cells function in HAM/TSP patients. It is suggested that activated MPs may be a therapeutic target for clinical intervention in HAM/TSP.</jats:p> </jats:sec>

Journal

  • Retrovirology

    Retrovirology 9 (1), 2012-02-15

    Springer Science and Business Media LLC

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