Abstract:
:Recruitment and extravasation of T cells through the blood-brain barrier are favored by adhesion molecule-mediated interactions of circulating T cells with endothelial cells. Since a common pathological finding in human T-cell leukemia virus type 1 (HTLV-1)-associated diseases is the infiltration of HTLV-1-infected T lymphocytes into various organs, we have looked for the profile of adhesion molecules expressed by HTLV-1-transformed T cells. Flow cytometry analysis indicated that these cells were expressing high levels of vascular cell adhesion molecule 1 (VCAM-1 [CD106]), a 110-kDa member of the immunoglobulin gene superfamily, first identified on endothelial cells stimulated with inflammatory cytokines. This adhesion molecule was also expressed by T cells obtained from one patient with HTLV-1-associated myelopathy/tropical spastic paraparesis but not by activated T cells isolated from one normal blood donor. The role of the viral trans-activator Tax protein in the induction of VCAM-1 was first indicated by the detection of this adhesion molecule on Jurkat T-cell clones stably expressing the tax gene. The effect of Tax on VCAM-1 gene transcription was next confirmed in JPX-9 cells, a subclone of Jurkat cells, carrying the tax sequences under the control of an inducible promoter. Furthermore, deletion and mutation analyses of the VCAM-1 promoter performed with chloramphenicol acetyltransferase constructs revealed that Tax was trans activating the VCAM-1 promoter via two NF-kappaB sites present at bp -72 and -57 in the VCAM-1 gene promoter, with both of them being required for the Tax-induced expression of this adhesion molecule. Finally, gel mobility shift assays demonstrated the nuclear translocation of proteins specifically bound to these two NF-kappaB motifs, confirming that VCAM-1 was induced on Tax-expressing cells in a kappaB-dependent manner. Collectively, these results therefore suggest that the exclusive Tax-induced expression of VCAM-1 on T cells may represent a pivotal event in the progression of HTLV-1-associated diseases.
journal_name
J Viroljournal_title
Journal of virologyauthors
Valentin H,Lemasson I,Hamaia S,Cassé H,König S,Devaux C,Gazzolo Ldoi
10.1128/JVI.71.11.8522-8530.1997subject
Has Abstractpub_date
1997-11-01 00:00:00pages
8522-30issue
11eissn
0022-538Xissn
1098-5514journal_volume
71pub_type
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pub_type: 杂志文章
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更新日期:1982-11-01 00:00:00
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journal_title:Journal of virology
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pub_type: 杂志文章
doi:10.1128/JVI.63.12.5354-5363.1989
更新日期:1989-12-01 00:00:00
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journal_title:Journal of virology
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doi:10.1128/JVI.69.1.357-364.1995
更新日期:1995-01-01 00:00:00
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更新日期:1999-06-01 00:00:00
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更新日期:2001-08-01 00:00:00
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pub_type: 杂志文章
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