Journal article
Extracellular Tax protein of human T cell leukemia virus type 1 activates monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell proliferation
Journal of neurovirology, Vol.12, pp.35-35
01 May 2006
Abstract
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by the generation of an intense cytotoxic T cell (CTL) response with large numbers of CD8+ CTLs directed against oncoprotein Tax. Previous studies suggest that Tax may be available for immune recognition by dendritic cells (DCs), the most efficient antigen presenting cell population. In this study, we have shown that purified Tax protein efficiently bound and localized to the cell membrane of monocyte-derived dendritic cells (MDDCs) and was internalized within a few hours. After uptake, Tax induced expression of DC activation markers MHC class I and II, and costimulatory molecules (CD40, CD80, CD86, and CD54) as well as the DC maturation marker, CD83. Tax has also promoted the production of major immune-directing cytokines IL-12, TNF-alpha, and proinflammatory chemokines MIP-1alpha, MIP-1beta, and RANTES, which drive a Th1-type immune response. The inhibitors of NF-kappaB have abrogated Tax-induced secretion of cytokines/chemokines indicating a role for NF-kappaB signaling in the Tax-mediated immune response. Finally, Tax enhanced the allogenic and antigen-specific T cell proliferation capability of MDDCs. These results indicate that extra-cellular Tax may selectively target MDDCs, be taken up by these cells most likely by specialized pathways, and promote their maturation and antigen-presenting functions, driving a Th1-type immune response.
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Details
- Title
- Extracellular Tax protein of human T cell leukemia virus type 1 activates monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell proliferation
- Creators
- P JainJ AhujaS ShimizuO MeucciZ KhanB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.12, pp.35-35
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170537504721