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Highly Enhanced Expression of CD70 on Human T-Lymphotropic Virus Type 1-Carrying T-Cell Lines and Adult T-Cell Leukemia Cells

Masanori Baba,^1,* Mika Okamoto,^1, Takayuki Hamasaki,¹ Sawako Horai,² Xin Wang,^1, Yuji Ito,³ Yasuo Suda,⁴ and Naomichi Arima²

Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan,¹ Division of Host Response, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan,² Department of Bioengineering, Faculty of Engineering, Kagoshima University, Kagoshima 890-0065, Japan,³ Nanostructured and Advanced Materials Course, Graduate School of Science and Engineering, Kagoshima University, Kagoshima 890-0065, Japan⁴

Received 11 September 2007/ Accepted 30 January 2008

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.

Published ahead of print on 6 February 2008.

These authors contributed equally to this work.

Present address: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520.