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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 (FCM) of CD83 expression on primary CD4+ T cells expressing Tax1. a, b Lymphocytes were gated based on FSC and SSC in peripheral blood mononuclear cells (PBMCs) derived from adult T cell leukemia (ATL) patients (ATL# 1 to #5) and examined for expression of CD83 and Tax1 before or after a 1-day culture. Most ATL patient-derived PBMCs consisted of leukemic CD4+ T cells (data not shown). c Lymphocytes in PBMCs from normal donors were examined for CD83 expression after a 1-day culture in the presence or absence of phytohemagglutinin (PHA). Representative profiles are displayed.
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Fig1: Flow cytometric analysis (FCM) of CD83 expression on primary CD4+ T cells expressing Tax1. a, b Lymphocytes were gated based on FSC and SSC in peripheral blood mononuclear cells (PBMCs) derived from adult T cell leukemia (ATL) patients (ATL# 1 to #5) and examined for expression of CD83 and Tax1 before or after a 1-day culture. Most ATL patient-derived PBMCs consisted of leukemic CD4+ T cells (data not shown). c Lymphocytes in PBMCs from normal donors were examined for CD83 expression after a 1-day culture in the presence or absence of phytohemagglutinin (PHA). Representative profiles are displayed.

Mentions: In a phenotypic analysis of fresh and in vitro cultured PBMCs from ATL patients in Okinawa, we noticed that short-term cultivation induced CD83 expression in a subpopulation of CD4+ T cells in PBMCs (Figure 1a, b). Interestingly, a majority of the CD83-positive CD4+ T cells exhibited detectable levels of intracellular Tax1 expression. The Tax1 expression in cultured PBMCs from ATL patients was confirmed by a western blot analysis with our anti-Tax1 monoclonal antibody (mAb) (Lt-4) (Additional file 1: Figure S1). Similar acquisition of CD83 on Tax1+ cells was observed in cultured PBMCs from HTLV-I carriers and HAM/TSP patients (data not shown). In contrast, only low levels of CD83 expression were observed in normal PBMCs cultured in vitro without mitogen. Cultures with mitogen exhibited increased CD83 expression in a small population of CD3- PBMCs (Figure 1c), which were predominantly CD19+ (data not shown), indicating that those CD83+ cells were B lymphocytes.Figure 1


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 (FCM) of CD83 expression on primary CD4+ T cells expressing Tax1. a, b Lymphocytes were gated based on FSC and SSC in peripheral blood mononuclear cells (PBMCs) derived from adult T cell leukemia (ATL) patients (ATL# 1 to #5) and examined for expression of CD83 and Tax1 before or after a 1-day culture. Most ATL patient-derived PBMCs consisted of leukemic CD4+ T cells (data not shown). c Lymphocytes in PBMCs from normal donors were examined for CD83 expression after a 1-day culture in the presence or absence of phytohemagglutinin (PHA). Representative profiles are displayed.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Flow cytometric analysis (FCM) of CD83 expression on primary CD4+ T cells expressing Tax1. a, b Lymphocytes were gated based on FSC and SSC in peripheral blood mononuclear cells (PBMCs) derived from adult T cell leukemia (ATL) patients (ATL# 1 to #5) and examined for expression of CD83 and Tax1 before or after a 1-day culture. Most ATL patient-derived PBMCs consisted of leukemic CD4+ T cells (data not shown). c Lymphocytes in PBMCs from normal donors were examined for CD83 expression after a 1-day culture in the presence or absence of phytohemagglutinin (PHA). Representative profiles are displayed.
Mentions: In a phenotypic analysis of fresh and in vitro cultured PBMCs from ATL patients in Okinawa, we noticed that short-term cultivation induced CD83 expression in a subpopulation of CD4+ T cells in PBMCs (Figure 1a, b). Interestingly, a majority of the CD83-positive CD4+ T cells exhibited detectable levels of intracellular Tax1 expression. The Tax1 expression in cultured PBMCs from ATL patients was confirmed by a western blot analysis with our anti-Tax1 monoclonal antibody (mAb) (Lt-4) (Additional file 1: Figure S1). Similar acquisition of CD83 on Tax1+ cells was observed in cultured PBMCs from HTLV-I carriers and HAM/TSP patients (data not shown). In contrast, only low levels of CD83 expression were observed in normal PBMCs cultured in vitro without mitogen. Cultures with mitogen exhibited increased CD83 expression in a small population of CD3- PBMCs (Figure 1c), which were predominantly CD19+ (data not shown), indicating that those CD83+ cells were B lymphocytes.Figure 1

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