International Journal of Hematology

DOI: 10.1007/s12185-018-02580-z Pages: 319-327

Association of high levels of plasma OX40 with acute adult T-cell leukemia

1. University of the Ryukyus, Department of Immunology, Graduate School of Medicine

2. Kawasaki Medical School, Department of Microbiology

3. University of the Ryukyus, Laboratory of Hematoimmunology, School of Health Sciences, Faculty of Medicine

Correspondence to:
Yuetsu Tanaka
Tel: 098-895-1202
Email: yuetsu@s4.dion.ne.jp

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Abstract

OX40, a member of the tumor necrosis factor receptor (TNFR) superfamily, co-stimulates activated T cells following interaction with its own ligand OX40L. Human T-cell leukemia virus type-1 (HTLV-1) is an etiological agent of adult T-cell leukemia (ATL). ATL cells are known to express cell surface OX40; however, the level of soluble OX40 (sOX40) in blood samples from ATL patients is unknown. Quantitative enzyme-linked immune-sorbent assay (ELISA) showed that sOX40 levels were significantly higher in plasma from acute ATL patients than those from asymptomatic HTLV-1 carriers and healthy donors, and correlated with sCD25 levels and HTLV-1 proviral loads in peripheral blood mononuclear cells (PBMCs). Fresh PBMCs from acute ATL patients showed a higher percentage of OX40-positive cells compared with those from carriers, and shed sOX40 into culture supernatants. Shedding of sOX40 was partially inhibited by a matrix metalloproteinase (MMP) inhibitor, GM6001. A fraction of sOX40 was capable of binding to OX40L. These results suggest that high levels of sOX40 are shed into blood from a large number of ATL cells in acute ATL patients. Thus, abnormally elevated plasma sOX40 levels may be useful as an additional diagnostic marker of acute ATL.

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