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 CX 3CR1 and HLA-DR in CD14 lowCD16 +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.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. © 2012 Enose-Akahata et al; licensee BioMed Central Ltd.