Use of human antigen presenting cell gene array profiling to examine the effect of human T-cell leukemia virus type 1 Tax on primary human dendritic cells

Department of Microbiology & Immunology, Drexel University, Filadelfia, Pennsylvania, United States
Journal of NeuroVirology (Impact Factor: 2.6). 03/2006; 12(1):47-59. DOI: 10.1080/13550280600614981
Source: PubMed


Human T-cell leukemia virus type 1 (HTLV-1) is etiologically linked to adult T-cell leukemia and a progressive demyelinating disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the most striking features of the immune response in HAM/TSP centers on the expansion of HTLV-1-specific CD8(+) cytotoxic T lymphocyte (CTL) compartment in the peripheral blood and cerebrospinal fluid. More than 90% of the HTLV-1-specific CTLs are directed against the viral Tax (11-19) peptide implying that Tax is available for immune recognition by antigen presenting cells, such as dendritic cells (DCs). DCs obtained from HAM/TSP patients have been shown to be infected with HTLV-1 and exhibit rapid maturation. Therefore, we hypothesized that presentation of Tax peptides by activated DCs to naIve CD8(+) T cells may play an important role in the induction of a Tax-specific CTL response and neurologic dysfunction. In this study, a pathway-specific antigen presenting cell gene array was used to study transcriptional changes induced by exposure of monocyte-derived DCs to extracellular HTLV-1 Tax protein. Approximately 100 genes were differentially expressed including genes encoding toll-like receptors, cell surface receptors, proteins involved in antigen uptake and presentation and adhesion molecules. The differential regulation of chemokines and cytokines characteristic of functional DC activation was also observed by the gene array analyses. Furthermore, the expression pattern of signal transduction genes was also significantly altered. These results have suggested that Tax-mediated DC gene regulation might play a critical role in cellular activation and the mechanisms resulting in HTLV-1-induced disease.

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Available from: Pooja Jain, Jan 29, 2016
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    • "Briefly, CD4 + and CD8 + T cells were purified from monocyte depleted PBMCs by using EasySep negative selection enrichment cocktail (StemCell Technologies, Vancouver, Canada). Dendritic cells (DCs) were differentiated from highly purified CD14 + monocytes as described (Ahuja et al., 2006) and maintained in complete RPMI medium supplemented with recombinant human granulocyte macrophagecolony stimulating factor (GM-CSF, 50 ng/ml, PeproTech; Rocky Hill, NJ) and interleukin-4 (IL-4, 10 ng/ml, PeproTech). "
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