Abstract
gp34, which we had identified as a target molecule of the trans‐activation by Tax of human T‐cell leukemia virus type I (HTLV‐I), has been found to bind OX40, a member of the tumor necrosis factor receptor family, resulting in growth stimulation of activated T cells. We here demonstrate that not only gp34 (OX40L), but also OX40 can be transcriptionally activated by Tax. Three Tax‐producing human T‐cell lines carrying the HTLV‐I genome expressed OX40 on their surfaces. Furthermore, Tax‐induced transcriptional activation of OX40 was shown in Tax‐inducible JPX‐9 cells. These results demonstrate that both OX40 and its ligand (gp34) are constitutively expressed on the surfaces of Tax‐expressing T lymphocytes, suggesting that the OX40L/OX40 system contributes to growth stimulation of the virus‐infected T cells.
Keywords: HTLV‐I, Tax, OX40, OX40 ligand
Full Text
The Full Text of this article is available as a PDF (287.7 KB).
REFERENCES
- 1. ) Sugamura , K. and Hinuma , Y.Human retroviruses: HTLV‐I and HTLV‐II . In “ The Retroviridae ,” Vol. 2 , ed. , Levy J. A. , pp. 399 – 435 ( 1993. ). Plenum Publ. Corp. , New York . [Google Scholar]
- 2. ) Sodroski , J. O. , Rosen , C. A. and Haseltine , W. A.Transacting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells . Science 225 , 381 – 385 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Sodroski , J. , Rosen , C. , Goh , W. C. and Haseltine , W. A.transcriptional activator protein encoded by the x‐lor region of the human T‐cell leukemia virus . Science 228 , 1430 – 1434 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Seiki , M. , Kiyokawa , T. and Yoshida , M.Functional activation of the long terminal repeat of human T‐cell leukemia virus type I by a trans‐acting factor . Proc. Natl. Acad. Sci. USA 82 , 2277 – 2281 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. ) Felber , B. K. , Paskalis , H. , Kleinman‐Ewing , C. , Wong‐Staal , F. and Pavlakis , G. N.The pX protein of HTLV‐I is a transcriptional activator of its long terminal repeats . Science 229 , 675 – 679 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Seiki , M. , Inoue , J. , Takeda , T. and Yoshida , M.Direct evidence that p40x of human T‐cell leukemia virus type I is a trans‐acting transcriptional activator . EMBO J. 5 , 561 – 565 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. ) Shimotono , K. , Takano , M. , Teruuchi , T. and Miwa , M.Requirement of multiple copies of a 21‐nucleotide sequence in the U3 regions of human T‐cell leukemia virus type I and type II long terminal repeats for transacting activation of transcription . Proc. Natl. Acad. Sci. USA 83 , 8112 – 8116 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Fujisawa , J. , Seiki , M. , Sato , M. and Yoshida , M.A transcriptional enhancer sequence of HTLV‐I is responsible for trans‐activation mediated by p40x of HTLV‐I . EMBO J. 5 , 713 – 718 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Fujii , M. , Sassone‐Corsi , P. and Verma , I. M.c‐fos promoter trans‐activation by tax1 protein of human T‐cell leukemia virus type I . Proc. Natl. Acad. Sci. USA 85 , 8526 – 8530 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Nagata , K. , Ohtani , K. , Nakamura , M. and Sugamura , K.Activation of endogenous c‐fos proto‐oncogene expression by human T‐cell leukemia virus type I‐encoded p40tax protein in human T‐cell line, Jurkat . J. Virol. 63 , 3220 – 3226 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Maruyama , M. , Shibuya , H. , Harada , H. , Hatakeyama , M. , Seiki , M. , Fujita , T. , Inoue , J. , Yoshida , M. and Taniguchi , T.Evidence for aberrant activation of the interleukin‐2 autocrine loop by HTLV‐I‐encoded p40x and T3/Ti complex triggering . Cell 48 , 343 – 350 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Siekevitz , M. , Feinberg , M. B. , Holbrook , N. , Wong‐Staal , F. and Greene , W.C.Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans‐activator (tat) gene product of human T‐cell leukemia virus, type I . Proc. Natl. Acad. Sci. USA 84 , 5389 – 5393 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Inoue , J. , Seiki , M. , Taniguchi , T. , Tsuru , S. and Yoshida , M.Induction of interleukin 2 receptor gene expression by p40x encoded by human T‐cell leukemia virus type I . EMBOJ. 5 , 2883 – 2888 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. ) Ohbo , K. , Takasawa , N. , Ishii , N. , Tanaka , N. , Nakamura , M. and Sugamura , K.Functional analysis of the human interleukin 2 receptor γ chain gene promoter . J. Biol. Chem. 270 , 7479 – 7486 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Tanaka , A. , Takahashi , C. , Yamaoka , S. , Nosaka , T. , Maki , M. and Hatanaka , M.Oncogenic transformation by the tax gene of human T‐cell leukemia virus type I in vitro . Proc. Natl. Acad. Sci. USA 87 , 1071 – 1075 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. ) Grassmann , R. , Dengler , C. , Müller‐Fleckenstein , I. , Fleckenstein , B. , McGuire , K. , Dokhelar , M.‐C. , Sodroski , J. and Haseltine , W.‐A.Transformation to continuous growth of primary human T lymphocytes by human T‐cell leukemia virus type I X‐region genes transduced by a Herpesvirus saimiri vector . Proc. Natl. Acad. Sci. USA 86 , 3351 – 3355 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. ) Nerenberg , M. , Steven , H. , Hinrichs , H. , Reynolds , R. K. , Khoury , G. and Jay , G.The tat gene of human T‐lymphotropic virus type 1 induces mesenchymal tumors in transgenie mice . Science 237 , 1324 – 1329 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Grossman , W. J. , Kimata , J. T. , Wong , F.‐H. , Zutter , M. , Ley , T. J. and Ratner , L.Development of leukemia in mice transgenic for tax gene of human T‐cell leukemia virus type I . Proc. Natl. Acad. Sci. USA 92 , 1057 – 1061 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. ) Tanaka , Y. , Inoi , T. , Tozawa , H. , Yamamoto , N. and Hinuma , Y.A glycoprotein antigen detected with new monoclonal antibodies on the surface of human lymphocytes infected with human T‐cell leukemia virus type‐I (HTLV‐I) . Int. J. Cancer 36 , 549 – 555 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Miura , S. , Ohtani , K. , Numata , N. , Niki , M. , Ohbo , K. , Ina , Y. , Gojobori , T. , Tanaka , Y. , Tozawa , H. , Nakamura , M. and Sugamura , K.Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T‐cell leukemia virus type I transactivator p40tax . Mol. Cell Biol. 11 , 1313 – 1325 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. ) Mallet , S. , Fossum , S. , and Barclay , A. N.Characterization of the MRC OX40 antigen of activated CD4 positive T lymphocytes, a molecule related to nerve growth factor receptor . EMBO J. 9 , 1063 – 1068 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. ) Latza , U. , Dürkop , H. , Schnittger , S. , Ringeling , J. , Eitelbach , F. , Hummel , M. , Fonatsch , C. and Stein , H.The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen . Eur. J. Immunol. 24 , 677 – 683 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Godfrey , W. R. , Faganoni , F. F. , Harara , M. A. , Buck , D. and Engleman , E. G.Identification of a human OX‐40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor . J. Exp. Med. 180 , 757 – 762 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. ) Baum , P. R. , Gayle , R. B. , III , Ramsdell , F. , Srinivasan , S. , Sorensen , R. A. , Watson , M. L. , Seldin , M. F. , Goodwin , R. G. and Fanslow , W. C.Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV‐1‐regulated protein gp34 . EMBO J. 13 , 3992 – 4001 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. ) Yaegashi , N. , Tada , K. , Shiraishi , H. , Ishii , T. , Nagata , K. and Sugamura , K.Characterization of monoclonal antibodies against human parvo virus B19 . Microbiol. Immunol. 33 , 561 – 567 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 26. ) Ohtani , K. , Nakamura , M. , Saito , S. , Nagata , K. , Sugamura , K. and Hinuma , Y.Electroporation: application to human lymphoid cell lines for stable introduction of a transactivator gene of human T‐cell leukemia virus type I . Nucleic Acids Res. 17 , 1589 – 1604 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. ) Tanaka , Y. , Tozawa , H. , Hayami , M. , Sugamura , K. and Hinuma , Y.Distinct reactivities of four monoclonal antibodies with human interleukin 2 receptor . Microbiol. Immunol. 29 , 959 – 972 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 28. ) Bollard , D. W. , Bohnlein , E. , Lowenthal , J. W. , Wano , Y. , Franza , B. R. and Greene , W. C.HTLV‐I tax induces cellular protein that activate the kB element in the IL‐2 receptor α gene . Science 241 , 1652 – 1655 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 29. ) Leung , K. and Nabel , G. J.HTLV‐I transactivator induces interleukin‐2 receptor expression through an NF‐kB‐like factor . Nature 333 , 776 – 778 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 30. ) Stüber , E. , Neurath , M. , Calderhead , D. , Fell , H. P. and Strober , W.Cross‐linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells . Immunity 2 , 507 – 521 ( 1995. ). [DOI] [PubMed] [Google Scholar]