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

Baba, Masanori; Okamoto, Masato; Hamasaki, Takayuki; Horai, Sawako; Wang, Xin; Ito, Yuji; Suda, Yasuo; Arima, Naomichi

doi:10.1128/jvi.02013-07

Cited by 33 publications

(29 citation statements)

References 43 publications

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“…5b) In the present study, we demonstrated that T cells acquire high levels of IRF-5 expression during HTLV-1 infection. Our results are consistent with those of oligonucleotide microarray reported by baba et al (46), who identified IRF-5 to be one of the genes that were upregulated more than 40-fold in three HTLV-1-infected T-cell lines, including MT-2, compared with uninfected T-cell line MOLT-4. Our results also showed that the oncoprotein Tax activated the IRF-5 V3 promoter, and that IRF-5 was expressed in ATL cells infiltrating the lymph nodes and skin.…”

Section: Irf-5 Targets Tnf Family Cytokine Genessupporting

confidence: 82%

Constitutive expression of IRF-5 in HTLV-1-infected T cells

Ishikawa

Senba

Barnes

et al. 2015

International Journal of Oncology

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Abstract. Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive and fatal leukemia of T cells. Interferon regulatory factor (IRF)-5 plays a critical role in the induction of interferon genes in viral infected cells. We examined the specific mechanisms underlying the expression and regulation of IRF-5 in HTLV-1-infected T cells. IRF-5 was constitutively transcribed into three distinct alternatively spliced isoforms (V1, V3 and V4) in HTLV-1-infected T-cell lines but not in uninfected T-cell lines. IRF-5 was also upregulated in HTLV-1-infected T-cell lines at protein level. Nuclear IRF-5 expression was noted in ATL cells present in lymph nodes and skin lesions. IRF-5 mRNA expression was induced following infection of T cells with HTLV-1, and specifically by viral oncoprotein Tax. Tax also activated V3 promoter. Microarray analysis of IRF-5-expressing uninfected T cells demonstrated that IRF-5 induced the expression of tumor necrosis factor family cytokines. The results suggest that IRF-5 is a Tax-regulated gene, and its expression may be associated with the pathogenesis of ATL.

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Section: Irf-5 Targets Tnf Family Cytokine Genessupporting

confidence: 82%

Constitutive expression of IRF-5 in HTLV-1-infected T cells

Ishikawa

Senba

Barnes

et al. 2015

International Journal of Oncology

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“…32,33 Although the proportion of CD4 þ CCR4 þ cells and CD4 þ CD70 þ cells in the PBMCs from healthy individuals were found to be approximately 5%, 27,33 the proportion of CD4 þ CADM1 þ cells was o1% ( Figure 2); therefore, measurement of CADM1 þ T cells is particularly efficient in the diagnosis of HTLV-1 infection in individuals who carry a small number of HTLV-1-infected cells. We have demonstrated previously that CADM1 has important functions in increasing cell adhesion and mediating progression to organ invasion.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of CADM1/TSLC1/IgSF4 expression in adult T-cell leukemia/lymphoma

et al. 2012

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Cell adhesion molecule 1 (CADM1/TSLC1) was recently identified as a novel cell surface marker for adult T-cell leukemia/ lymphoma (ATLL). In this study, we developed various antibodies as diagnostic tools to identify CADM1-positive ATLL leukemia cells. In flow cytometric analysis, the percentages of CD4 þ CADM1 þ double-positive cells correlated well with both the percentages of CD4 þ CD25 þ cells and with abnormal lymphocytes in the peripheral blood of patients with various types of ATLL. Moreover, the degree of CD4 þ CADM1 þ cells over 1% significantly correlated with the copy number of the human T-lymphotropic virus type 1 (HTLV-1) provirus in the peripheral blood of HTLV-1 carriers and ATLL patients. We also identified a soluble form of CADM1 in the peripheral blood of ATLL patients, and the expression levels of this form were correlated with the levels of soluble interleukin 2 receptor alpha. Moreover, lymphomas derived from ATLL were strongly and specifically stained with a CADM1 antibody. Thus, detection of CD4 þ CADM1 þ cells in the peripheral blood, measurement of serum levels of soluble CADM1 and immunohistochemical detection of CADM1 in lymphomas would be a useful set of markers for disease progression in ATLL and may aid in both the early diagnosis and measurement of treatment efficacy for ATLL.

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“…We found that CD25, CD70, and CD80 are both localized at VB and upregulated by Tax. The Tax-inducible expression of these antigens has been reported earlier (Baba et al, 2008;Ballard et al, 1988;Dezzutti et al, 1995). However, the role of such upregulation in HTLV-1 pathogenesis remains unknown.…”

Section: Discussionmentioning

confidence: 91%

“…We examined the levels of CD antigen expression on Jurkat T cells transduced with Tax. Consisting with the previous reports, we found the inducible patterns of expression for CD25 (Ballard et al, 1988;Ruben et al, 1988), CD54 (Mori et al, 1994), and CD70 (Baba et al, 2008) antigens. In addition, we found that Tax induced expression of CD80, a novel observation.…”

Section: Introductionmentioning

confidence: 86%

“…Interacting with transcription factors, signaling and transport molecules, cytoskeleton, PDZ proteins and other intracellular messengers, Tax induces global changes in the cellular transcriptome (reviewed in (Boxus et al, 2008)) as was demonstrated at the level of mRNA (Baba et al, 2008; The levels of CD antigen expression in Tax-positive cells relative to Tax-negative cells were calculated as the mean fluorescence intensity for PE in region 3 (R3) divided by the mean fluorescence intensity for PE in region 2 (R2); gating for regions R2 and R3 is shown in the left panel of Fig. 5a.…”

Section: Discussionmentioning

confidence: 99%

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Monoclonal antibody profiling of cell surface proteins associated with the viral biofilms on HTLV-1 transformed cells

Tarasevich¹,

Filatov²,

Пичугин³

et al. 2015

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Summary. -Human T lymphotropic virus 1 (HTLV-1) is a pathogenic retrovirus that spreads predominantly via cell-to-cell contact. Two models of cell-to-cell virus transmission are proposed: virological synapse (VS) and viral biofilms (VB). Both infectious structures can be involved in transmission and synergistically enhance HTLV-1 spread between cells. Although transmission of virus via VB has been reported, the molecular composition of VB remains poorly understood. In this study we generated new anti-VB monoclonal antibodies (MAbs) and screened them along with a panel of anti-human cluster of differentiation (CD) MAbs to select antigens associated with VB. Among four MAbs generated against VB, two MAbs were identified as anti-CD25 (IL-2RA). We found that antigens CD4, CD150, CD25, CD70, and CD80 were enriched in VB. We also determined that expression of viral protein Tax, a central molecule in HTLV-1 transmission, upregulates intercellular adhesion molecule 1 (ICAM-1), CD95, CD25, CD70, and CD80. Whether these antigens are essential for VB formation and HTLV-1 infection remains unknown and will be determined in further experiments.Keywords: monoclonal antibody; CD antigen; HTLV-1; biofilms * Corresponding author. E-mail: dvmazurov@yandex.ru; phone: +74996128854. Abbreviations: CD = cluster of differentiation; HIV-1 = human immunodeficiency virus 1; HTLV-1 = human T cell lymphotropic virus 1; ICAM-1 = intercellular adhesion molecule 1; IL-2-RA = interleukin 2 receptor subunit A; IP = immunoprecipitation; MAb(s) = monoclonal antibody(ies); MS = mass-spectrometry; PE = phycoerythrin; TM4SF = transmembrane 4 superfamily proteins; VB = viral biofilms; VS = virological synapse; WB = Western blot; Wt = wild type

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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

Cited by 33 publications

References 43 publications

Constitutive expression of IRF-5 in HTLV-1-infected T cells

Constitutive expression of IRF-5 in HTLV-1-infected T cells

Clinical significance of CADM1/TSLC1/IgSF4 expression in adult T-cell leukemia/lymphoma

Monoclonal antibody profiling of cell surface proteins associated with the viral biofilms on HTLV-1 transformed cells

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