Journal article
Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1: Implications for HTLV-1-associated neuroinflammatory disease
Journal of neurovirology, Vol.13, pp.88-88
01 Jan 2007
Abstract
HTLV-1-associated myelopathy/tropical spastic para-paresis (HAM/TSP) is characterized by the generation of an intense cytotoxic T cell (CTL) response directed against the viral transactivator protein Tax. Additionally, patients diagnosed with HAM/TSP exhibit rapid activation and maturation of dendritic cells (DCs] likely contributing to the robust Tax-specific CTL response. In this study, extracellular Tax has been shown to induce maturation and functional alterations in human monocyte-derived DCs, critical observations being confirmed in freshly isolated myeloid DCs. Tax was shown to promote the production of proinflammatory cytokines and chemokines involved in DC activation process in a dose- and time-dependent manner. Furthermore, Tax induced the expression of DC activation (CD40, CD80, and CD86) and maturation (CD83) markers and enhanced the allogenic and antigen-specific T cell proliferation capability of DCs. Heat inactivation of Tax resulted in abrogation of these effects indicating a requirement for the native structure of Tax. Tax was found to efficiently bind to the DC membrane and was internalized within a few hours suggesting that extracellular Tax may possess an intracellular mechanism of action subsequent to entry. Finally, inhibitors of cellular signaling pathways NF-kappaB, protein kinase, tyrosine kinase and phospholipase C were shown to inhibit Tax-mediated DC activation. This is the first study reporting the immunomodulatory effects of extracellular Tax in the DC compartment. These results suggest that DCs, once exposed to Tax by uptake from the extracellular environment, can undergo activation providing constant antigen presentation and costimulation to T cells leading to the intense T cell proliferation and inflammatory responses underlying HAM/TSP. Ongoing ex vivo investigations include frequency, activation state, and functions of various DC subsets in HAM/TSP patients.
Metrics
2 Record Views
Details
- Title
- Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1: Implications for HTLV-1-associated neuroinflammatory disease
- Creators
- P JainJ AhujaZ KhanS ShimizuO MeucciS R JenningsB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.13, pp.88-88
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170569004721