Journal article
Induction of proinflammatory cytokines by human T cell leukemia virus type 1 Tax protein as determined by multiplexed cytokine protein array analyses of human monocyte-derived dendritic cells
Journal of neurovirology, Vol.13, pp.60-60
01 Jan 2007
Abstract
Human T cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by a hyperstimulated immune response including elevated levels of inflammatory cytokines/chemokines, and the oligoclonal expansion of virus-specific CD8+ T cells in the cerebrospinal fluid. Studies have shown that the HTLV-1 transactivator protein Tax is available for immune recognition by antigen presenting cells (APCs) such as dendritic cells (DCs). DCs are relevant to the pathogenesis of HAM/TSP since the presentation of Tax peptides by activated DCs to naive CD8+ T cells may play an important role in the induction of a Tax-specific immune responses observed in HAM/TSP. In this study, a human cytokine protein array was used to study the secretion of cytokines by monocyte-derived DCs (MDDCs) exposed to Tax. Of the 16 cytokines analyzed, 6 cytokines were secreted in significantly high amounts ( similar to 2-fold) including Th1 cytokines (IFN-gamma, IL-12, and TNF-alpha) and C-C chemokines (Eotaxin, MCP-1, and MCP-3). Selected cytokines were further examined at two concentrations of Tax and two time periods. Furthermore, a transient exposure to Tax did not result in any cytokine production when examined at three different time points after exposure, indicating that the prolonged presence of Tax was required for its activity. Finally, inhibition of the NF-kappaB signaling pathway by specific inhibitors abrogated Tax-mediated cytokine secretion. Collectively, these investigations suggest that Tax-induced cytokine secretion from MDDCs may be an important factor in the cellular activation and tissue damage observed in HAM/TSP.
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Details
- Title
- Induction of proinflammatory cytokines by human T cell leukemia virus type 1 Tax protein as determined by multiplexed cytokine protein array analyses of human monocyte-derived dendritic cells
- Creators
- J AhujaV LepoutreB WigdahlZ KhanP Jain
- Publication Details
- Journal of neurovirology, Vol.13, pp.60-60
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170579904721