%0 Journal Article
%T Minocycline modulates antigen-specific CTL activity through inactivation of mononuclear phagocytes in patients with HTLV-I associated neurologic disease
%A Yoshimi Enose-Akahata
%A Eiji Matsuura
%A Yuetsu Tanaka
%A Unsong Oh
%A Steven Jacobson
%J Retrovirology
%D 2012
%I BioMed Central
%R 10.1186/1742-4690-9-16
%X 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-¦Á and IL-1¦Â 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-¦Á expression in CD14+ cells and IL-1¦Â release in PBMCs of HAM/TSP patients. Minocycline significantly inhibited spontaneous lymphoproliferation and degranulation/IFN-¦Ã expression in CD8+ T cells of HAM/TSP patients. Treatment of minocycline also inhibited IFN-¦Ã expression in CD8+ T cells of HAM/TSP patients after Tax11-19 stimulation and downregulated MHC class I expression in CD14+ cells.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.The human T cell lymphotropic virus I (HTLV-I) infects 20 million people worldwide of which the majority of infected individuals are asymptomatic carriers (AC) of the virus [1]. However, in a small percentage of infected individuals, HTLV-I is the etiologic agent of adult T cell leukemia/lymphoma (ATL) [2] and a chronic, progressive neurological disease termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [3,4]. Patients with HAM/TSP demonstrate high HTLV-I proviral DNA load, high HTLV-I Tax mRNA load, and high virus-specific immune responses, including increased production of inflammatory cytokines and expansion of Tax-specific CD8+ T cells [5-9]. A high frequency of CD4+ T cells is persistently infected and exhibits high expression of Tax protein [10]. These infected cells are responsible for the increased lymphocyte proliferation in patients wi
%K HTLV-I
%K HAM/TSP
%K monocyte
%K CTL
%K minocycline
%U http://www.retrovirology.com/content/9/1/16