Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.

Grossman, William; Kimata, Jason T.; Wong, Fen Hwa; Zutter, Mary M.; Ley, Timothy J.; Ratner, Lee

doi:10.1073/pnas.92.4.1057

Cited by 350 publications

(311 citation statements)

References 26 publications

Supporting

Mentioning

305

Contrasting

Order By: Relevance

“…Adhesion molecules on leukemic LGL might also affect the infiltrating capacities of these cells, presuming differences in their invasive potential. These results are in line with LGL leukemia observed in mice transgenic for HTLV-I Tax, 40 although the involvement of HTLV-I or -II in nonaggressive T cell leukemia remains controversial. 41,42 Moreover, this upregulation of adhesion molecules is also in accordance with surface overexpression of various late activation markers such as HLA-DR and CD38 and with downmodulation of CD62L.…”

Section: Discussionsupporting

confidence: 79%

“…10,11 Of note, these leukemic cells also produce IFN-␥ after CD3 activation; so do LGL cell lines derived from the tail tumors of transgenic mice for Tax protein. 40 On the contrary, as already reported, 32 we show that unstimulated leukemic CD8 + CD57 + cells are unable to kill either K562 target cells of NK lysis or Daudi target cells of LAK lysis. Thus despite their LGL morphology and a CD16 and CD57 expression similar to NK cells, CD8 + CD57 + T lymphocytes from both T-LGL leukemic patients and BMT recipients are efficient CTLs but definitely…”

Section: Figuresupporting

confidence: 77%

See 1 more Smart Citation

Leukemic CD3+ LGL share functional properties with their CD8+CD57+ cell counterpart expanded after BMT

et al. 1999

View full text Add to dashboard Cite

Leukemic T-LGL (large granular lymphocyte) composed of clonal CD3 + TCR␣␤ + CD8 ؉ CD57 ؉ cells were compared with oligoclonally CD3 ؉ CD8 hi؉ CD57 ؊ lymphocytes expanded after BMT. Leukemic CD3 ؉ CD8 hi؉ CD57 ؉ LGL showed several phenotypic differences such as an upregulation of CD16 and adhesion molecules (mainly CD11c, CD58 and CD54), activation markers and an exclusive CD45RA isoform expression. Unstimulated CD3 ؉ CD8 ؉ CD57 ؉ LGL from both leukemic and BMT donors spontaneously developed an ex vivo CTL-like CD3-redirected cytotoxicity but no NK cell activity. Different stimuli (PHA, PMA or rhIL-2) induced similar cytotoxic profiles after a 6-day culture involving a CD3-redirected lysis predominating over a low NK cell activity. However, culture of leukemic LGL with these stimuli allowed either a 2 week persistence (PMA or rhIL-2) of CD8 ؉ CD57 ؉ LGL or their disappearance after 3 days (PHA). Furthermore, leukemic CD8 hi؉ CD57 ؉ T lymphocytes produced an inhibitor of cytotoxic functions as previously described for BMT recipients' CD8 ؉ CD57 ؉ cells. Thus, despite some phenotypic differences between both cell sources, leukemic CD57 ؉ T-LGL display the same functional characteristics of cytotoxic effector and immunoregulatory T cells as CD8 ؉ CD57 ؉ T cells from BMT recipients which might represent their normal counterpart.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Figuresupporting

confidence: 77%

Leukemic CD3+ LGL share functional properties with their CD8+CD57+ cell counterpart expanded after BMT

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Wild-type Tax1 can also convert IL-2-dependent murine CTLL cells to an IL-2-independent stage (Iwanaga et al, 1999). Finally, Tax1 transgenic animals expressing Tax under the control of the granzyme B promoter develop peripheral lymphomas consisting of CD8 þ and natural killer cells (Grossman et al, 1995). Tax1 interacts with transcription factors and activates the cyclic-AMP response element and activating transcription factor (ATF) binding (CREB/ATF) pathway, the NF-kB pathway and the serum response factor (SRF) pathway.…”

Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

View full text Add to dashboard Cite

Human T-cell leukemia virus and simian T-cell leukemia virus (STLV) form the primate T-cell lymphotropic viruses group. Human T-cell leukemia virus type 1 and type 2 (HTLV-1 and HTLV-2) encode the Tax viral transactivator (Tax1 and Tax2, respectively). Tax1 possesses an oncogenic potential and is responsible for cell transformation both in vivo and in vitro. We and others have recently discovered the existence of human Tcell lymphotropic virus type 3. However, there is currently no evidence for the presence of a Tax protein in HTLV-3-infected individuals. We show that the serum of an HTLV-3 asymptomatic carrier and the sera of two STLV-3-infected monkeys contain specific anti-Tax3 antibodies. We also show that tax3 mRNA is present in the PBMCs obtained from an STLV-3-infected monkey, demonstrating that Tax3 is expressed in vivo. We further demonstrate that Tax3 intracellular localization is very similar to that of Tax1 and that Tax3 binds to both CBP and p300 coactivators. Using purified Tax3, we show that the protein increases transcription from a 4TxRE G-free cassette plasmid in an in vitro transcription assay. In all cell types tested, including transiently transfected lymphocytes, Tax3 activates its own promoter STLV-3 long terminal repeat (LTR), which contains only two Tax Responsive Elements (TREs), and activates also HTLV-1 and HTLV-2 LTRs. In addition, Tax3 also activates the NF-jB pathway. We also show that Tax3 possesses a PDZ-binding sequence at its C-terminal end. Our results demonstrate that Tax3 is a transactivator, and that its properties are more similar to that of Tax1, rather than of Tax2. This suggests the possible occurrence of lymphoproliferative disorders among HTLV-3-infected populations.

show abstract

“…Tax increases the rate of transcription from the viral long terminal repeat (LTR) (Cann et al, 1985;Felber et al, 1985;Inoue et al, 1987) and modulates the transcription or activity of numerous cellular genes involved in cell growth and differentiation, cell cycle control, and DNA repair (Leung and Nabel, 1988;Mulloy et al, 1998;Ressler et al, 1997;Schmitt et al, 1998;Siekevitz et al, 1987). Compelling evidence indicates that the pleiotropic effects of Tax on cellular processes are required for the transforming or oncogenic capacity of HTLV (Endo et al, 2002;Grossman et al, 1995;Robek and Ratner, 1999;Ross et al, 2000;Ross et al, 1996;Wycuff and Marriott, 2005). Rex acts posttranscriptionally by preferentially binding, stabilizing, and selectively exporting introncontaining viral mRNAs from the nucleus to the cytoplasm (Younis and Green, 2005).…”

Section: Introductionmentioning

confidence: 99%

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Green

2007

Journal of Virological Methods

View full text Add to dashboard Cite

SummaryHTLV-1 and HTLV-2 are highly related delta-retroviruses that infect and transform T-lymphocytes, but have distinct pathogenic properties. HTLV replication and survival requires the expression of multiple gene products from an unspliced and a series of highly related alternatively spliced mRNA species. To date, the comparative levels of all known HTLV-1 and HTLV-2 viral mRNAs in different transformed cell lines and at different stages of virus infection have not been assessed. In this study, we compiled a series of oligonucleotide primer pairs and probes to quantify both HTLV-1 and HTLV-2 mRNA species using real-time RT-PCR. The optimized reaction for detection of each mRNA had amplification efficiency greater than 90% with a linear range spanning 25 to 2.5 × 10 7 copies. The R 2 s of all standard curves were greater than 0.97. Quantitation of HTLV mRNAs between different cell lines showed variability (gag/pol ≥ tax/rex > env ≥ accessory proteins), but the overall levels of each mRNA relative to each other within a cell line were similar. These results provide a method to quantify all specific mRNAs from both HTLV-1 and HTLV-2, which can be used to evaluate further viral gene expression and correlate transcript levels to key stages of the virus life cycle and ultimately, pathogenesis.

show abstract

Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.

Cited by 350 publications

References 26 publications

Leukemic CD3+ LGL share functional properties with their CD8+CD57+ cell counterpart expanded after BMT

Leukemic CD3+ LGL share functional properties with their CD8+CD57+ cell counterpart expanded after BMT

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Contact Info

Product

Resources

About