Human T-cell leukemia virus type-I Tax induces the expression of CD83 on T cells

• Authors: Yuetsu Tanaka, University of the Ryukyus; Mariko Mizuguchi, Tokyo Medical and Dental University; Yoshiaki Takahashi, University of the Ryukyus; Hideki Fujii, University of the Ryukyus; Reiko Tanaka, University of the Ryukyus; Takuya Fukushima, University of the Ryukyus; Takeaki Tomoyose, University of Ryukyus; Aftab Ansari, Emory University; Masataka Nakamura, Tokyo Medical and Dental University
• Journal Title: Retrovirology
• Volume: Volume 12, Number 56
• Publisher: BioMed Central | 2015-07-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/s12977-015-0185-1
• Subjects: Biology, Virology; Health Sciences, Immunology; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Virology; CD83; HTLV; Tax; ATL; PGE2; NF-KAPPA-B; ACTIVATED DENDRITIC CELLS; SOLUBLE CD83; TRANSCRIPTIONAL ACTIVATOR; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; HUMAN RETROVIRUS; HUMAN-SERA; LYMPHOCYTES; ANTIBODIES

Abstract

Background: CD83, a cell surface glycoprotein that is stably expressed on mature dendritic cells, can be transiently induced on other hematopoietic cell lineages upon cell activation. In contrast to the membrane form of CD83, soluble CD83 appears to be immunosuppressive. In an analysis of the phenotype of leukemic CD4+ T cells from patients with adult T-cell leukemia (ATL), we found that a number of primary CD4+ T cells became positive for cell surface CD83 after short-term culture, and that most of these CD83+ CD4+ T cells were positive for human T-cell leukemia virus type-I (HTLV-I) Tax (Tax1). We hypothesized that Tax1 is involved in the induction of CD83. Result: We found that CD83 was expressed selectively on Tax1-expressing human CD4+ T cells in short-term cultured peripheral blood mononuclear cells (PBMCs) isolated from HTLV-I+ donors, including ATL patients and HTLV-I carriers. HTLV-I-infected T cell lines expressing Tax1 also expressed cell surface CD83 and released soluble CD83. CD83 can be expressed in the JPX-9 cell line by cadmium-mediated Tax1 induction and in Jurkat cells or PBMCs by Tax1 introduction via infection with a recombinant adenovirus carrying the Tax1 gene. The CD83 promoter was activated by Tax1 in an NF-κB-dependent manner. Based on a previous report showing soluble CD83-mediated prostaglandin E2 (PGE2) production from human monocytes in vitro, we tested if PGE2 affected HTLV-I propagation, and found that PGE2 strongly stimulated expression of Tax1 and viral structural molecules. Conclusions: Our results suggest that HTLV-I induces CD83 expression on T cells via Tax1 -mediated NF-κB activation, which may promote HTLV-I infection in vivo.