title: Highly enhanced expression of CD70 on human T-lymphotropic virus type 1-carrying T-cell lines and adult T-cell leukemia cells.
abstract: Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). In Japan, the number of HTLV-1 carriers is estimated to be 1.2 million and more than 700 cases of ATL have been diagnosed every year. Considering the poor prognosis and lack of curative therapy of ATL, it seems mandatory to establish an effective strategy for the treatment of ATL. In this study, we attempted to identify the cell surface molecules that will become suitable targets of antibodies for anti-ATL therapy. The expression levels of approximately 40,000 host genes of three human T-cell lines carrying HTLV-1 genomes were analyzed by oligonucleotide microarray and compared with the expression levels of the genes in an HTLV-1-negative T-cell line. The HTLV-1-carrying T-cell lines used for experiments had totally different expression patterns of viral genome. Among the genes evaluated, the expression levels of 108 genes were found to be enhanced more than 10-fold in all of the T-cell lines examined and 11 of the 108 genes were considered to generate the proteins expressed on the cell surface. In particular, the CD70 gene was upregulated more than 1,000-fold and the enhanced expression of the CD70 molecule was confirmed by laser flow cytometry for various HTLV-1-carrying T-cell lines and primary CD4(+) T cells isolated from acute-type ATL patients. Such expression was not observed for primary CD4(+) T cells isolated from healthy donors. Since CD70 expression is strictly restricted in normal tissues, such as highly activated T and B cells, CD70 appears to be a potential target for effective antibody therapy against ATL.
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan. m-baba@vanilla.ocn.ne.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
authors.forename: Mika
authors.initials: M
authors.lastname: Okamoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamasaki
authors.forename: Sawako
authors.initials: S
authors.lastname: Horai
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ito
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suda
authors.forename: Naomichi
authors.initials: N
authors.lastname: Arima
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis; D053282:CD27 Ligand / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007564:Japan; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000737:chemistry* / Q000821:virology*; D015854:Up-Regulation; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D000954:Antigens, Surface; D053282:CD27 Ligand; D014764:Viral Proteins