Journal
RETROVIROLOGY
Volume 9, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/1742-4690-9-16
Keywords
HTLV-I; HAM/TSP; monocyte; CTL; minocycline
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Funding
- NINDS, NIH
- Grants-in-Aid for Scientific Research [221S0001] Funding Source: KAKEN
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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 CX(3)CR1 and HLA-DR in CD14(low)CD16(+) monocytes, compared to healthy normal donors (NDs) and asymptomatic carriers (ACs), and the production of TNF-alpha and IL-1 beta 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-alpha expression in CD14(+) cells and IL-1 beta release in PBMCs of HAM/TSP patients. Minocycline significantly inhibited spontaneous lymphoproliferation and degranulation/IFN-gamma expression in CD8(+) T cells of HAM/TSP patients. Treatment of minocycline also inhibited IFN-gamma expression in CD8(+) T cells of HAM/TSP patients after Tax11-19 stimulation and downregulated MHC class I expression in CD14(+) cells. Conclusion: 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.
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