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

Tanaka Y, Mizuguchi M, Takahashi Y, Fujii H, Tanaka R, Fukushima T, Tomoyose T, Ansari AA, Nakamura M - Retrovirology (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. yuetsu@s4.dion.ne.jp.

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.

No MeSH data available.


Related in: MedlinePlus

Flow cytometric analysis of Tax1 expression of cell sorter purified CD83hi/OX40hi and CD83negative/OX40negative populations. An IL-2 dependent HTLV-I+ T cell line generated from a HAM/TSP patient (OKH4) was stained with anti-OX40 and anti-CD83 mAbs. The CD83+OX40+ and CD83−OX40− populations were sorted, and stained for Tax1. The Tax1 expression profiles prior to and post sorting are shown.
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Fig7: Flow cytometric analysis of Tax1 expression of cell sorter purified CD83hi/OX40hi and CD83negative/OX40negative populations. An IL-2 dependent HTLV-I+ T cell line generated from a HAM/TSP patient (OKH4) was stained with anti-OX40 and anti-CD83 mAbs. The CD83+OX40+ and CD83−OX40− populations were sorted, and stained for Tax1. The Tax1 expression profiles prior to and post sorting are shown.

Mentions: It may be noteworthy that the triple-positive (Tax1+ CD83+ OX40+) phenotype was found in primary CD4+ T cells from an ATL patient (Figure 6). Generally, IL-2-dependent HTLV-I-infected T cell lines derived from HTLV-I+ donors consist of HTLV-I antigen-positive and -negative cells, especially during the early culture stage with low passages. Flow cytometry-based cell sorting cannot separate live Tax1+ cells from live Tax1− cells owing to intracellular localization of Tax1. Based on the present finding that most Tax1+ cells expressed both CD83 and OX40, we attempted to sort live Tax1+ and Tax1− cells. An IL-2 dependent HTLV-I+ T cell line (OKH4) from a HAM/TSP patient was stained with anti-OX40 and anti-CD83 mAbs, and subjected to cell sorting. CD83+ OX40+ sorting efficiently enriched the Tax1+ cell population (Figure 7). Similar enrichment of Tax1+ cells was obtained with three IL-2-dependent HTLV-I+ T cell lines (data not shown). This strategy would be useful for further studies on Tax1 function in pHTLV-I-infected primary T cells.Figure 6


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

Tanaka Y, Mizuguchi M, Takahashi Y, Fujii H, Tanaka R, Fukushima T, Tomoyose T, Ansari AA, Nakamura M - Retrovirology (2015)

Flow cytometric analysis of Tax1 expression of cell sorter purified CD83hi/OX40hi and CD83negative/OX40negative populations. An IL-2 dependent HTLV-I+ T cell line generated from a HAM/TSP patient (OKH4) was stained with anti-OX40 and anti-CD83 mAbs. The CD83+OX40+ and CD83−OX40− populations were sorted, and stained for Tax1. The Tax1 expression profiles prior to and post sorting are shown.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487981&req=5

Fig7: Flow cytometric analysis of Tax1 expression of cell sorter purified CD83hi/OX40hi and CD83negative/OX40negative populations. An IL-2 dependent HTLV-I+ T cell line generated from a HAM/TSP patient (OKH4) was stained with anti-OX40 and anti-CD83 mAbs. The CD83+OX40+ and CD83−OX40− populations were sorted, and stained for Tax1. The Tax1 expression profiles prior to and post sorting are shown.
Mentions: It may be noteworthy that the triple-positive (Tax1+ CD83+ OX40+) phenotype was found in primary CD4+ T cells from an ATL patient (Figure 6). Generally, IL-2-dependent HTLV-I-infected T cell lines derived from HTLV-I+ donors consist of HTLV-I antigen-positive and -negative cells, especially during the early culture stage with low passages. Flow cytometry-based cell sorting cannot separate live Tax1+ cells from live Tax1− cells owing to intracellular localization of Tax1. Based on the present finding that most Tax1+ cells expressed both CD83 and OX40, we attempted to sort live Tax1+ and Tax1− cells. An IL-2 dependent HTLV-I+ T cell line (OKH4) from a HAM/TSP patient was stained with anti-OX40 and anti-CD83 mAbs, and subjected to cell sorting. CD83+ OX40+ sorting efficiently enriched the Tax1+ cell population (Figure 7). Similar enrichment of Tax1+ cells was obtained with three IL-2-dependent HTLV-I+ T cell lines (data not shown). This strategy would be useful for further studies on Tax1 function in pHTLV-I-infected primary T cells.Figure 6

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. yuetsu@s4.dion.ne.jp.

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.

No MeSH data available.


Related in: MedlinePlus