title: GITR overexpression on CD4+CD25+ HTLV-1 transformed cells: detection by massively parallel signature sequencing.
abstract: HTLV-I is the etiologic agent of adult T-cell leukemia (ATL), a fatal T-cell malignancy that is associated with profound immunosuppression. In this study, comprehensive gene expression profiling was performed using massively parallel signature sequencing (MPSS) to investigate virus-host interactions in acutely HTLV-1 transformed cells. The analysis revealed the modulation of numerous genes across different functional classes, many of which have not been previously implicated in HTLV-1 transformation or ATL. Differences in the transcriptomes of transformed cell lines were observed that have provided clues on how different clonal populations of cells respond to virus transformation. Quantitation of HTLV-1 transcription was possible, thus making MPSS a useful tool to study emerging pathogens and unknown microbial causes of human diseases. Importantly, overexpression of GITR, an activation marker that has not been previously reported to be upregulated by HTLV-1-infection or in transformed/leukemic cells and that is associated with the suppressor phenotype of CD4+CD25+ regulatory T-cells (Tregs), was also observed. The deep and quantitative gene expression profile generated by MPSS should provide additional leads for discovery research that can be applied to better understand the pathobiology of HTLV-1 transformation and ATL as well as to developing new therapies.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, MA 02115, USA.
authors.forename: Harshawardhan P
authors.initials: HP
authors.lastname: Bal
authors.forename: Jihua
authors.initials: J
authors.lastname: Cheng
authors.forename: Akikazu
authors.initials: A
authors.lastname: Murakami
authors.forename: Aimee St Claire
authors.initials: AS
authors.lastname: Tallarico
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Daixing
authors.initials: D
authors.lastname: Zhou
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Vasicek
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
mesh_terms: D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral / Q000235:genetics*; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology*
chemical_list: D015704:CD4 Antigens; D053450:Glucocorticoid-Induced TNFR-Related Protein; D020543:Proteome; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human