Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Sep;80(17):5402–5406. doi: 10.1073/pnas.80.17.5402

Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus.

M Popovic, G Lange-Wantzin, P S Sarin, D Mann, R C Gallo
PMCID: PMC384264  PMID: 6604273

Abstract

Several isolates of human T-cell leukemia/lymphoma virus (HTLV) were transmitted to normal human T cells obtained from the umbilical cord blood of newborns. T cells from seven specimens were immortalized by infection with different HTLV isolates and their properties were compared with those of activated uninfected normal T cells grown in the presence of T-cell growth factor (TCGF) and with those of HTLV-positive neoplastic T-cell lines derived from patients with T-cell malignancies. The HTLV-infected cells generally belonged to a class of mature T cells (OKT4+ and Leu 3A+) and differed from the normal uninfected cells in that they could be propagated in culture indefinitely; possessed altered morphology, including convoluted nuclei and some bi- and multinucleated giant cells; formed large clumps in culture; demonstrated a diminished requirement for TCGF; had an increased density of TCGF receptors; often became completely independent of exogenous TCGF; and expressed HLA-DR determinants. These properties of the HTLV-infected cord blood T cells contrasted to those of uncultured cord blood T cells and of cord blood cells stimulated with mitogen and grown with TCGF but resembled the characteristics of T-cell lines established previously from patients with HTLV-associated T-cell malignancies. This in vitro system offers a unique opportunity to study the basic mechanism involved in abnormal growth and neoplastic transformation of a specific class of human T cells.

Full text

PDF
5402

Images in this article

5403Image
on p.5403
5403Image
on p.5403
5403Image
on p.5403
5403Image
on p.5403
5403Image
on p.5403
5403Image
on p.5403
5404Image
on p.5404
5404Image
on p.5404

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blattner W. A., Kalyanaraman V. S., Robert-Guroff M., Lister T. A., Galton D. A., Sarin P. S., Crawford M. H., Catovsky D., Greaves M., Gallo R. C. The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma. Int J Cancer. 1982 Sep 15;30(3):257–264. doi: 10.1002/ijc.2910300302. [DOI] [PubMed] [Google Scholar]
  2. Catovsky D., Greaves M. F., Rose M., Galton D. A., Goolden A. W., McCluskey D. R., White J. M., Lampert I., Bourikas G., Ireland R. Adult T-cell lymphoma-leukaemia in Blacks from the West Indies. Lancet. 1982 Mar 20;1(8273):639–643. doi: 10.1016/s0140-6736(82)92200-0. [DOI] [PubMed] [Google Scholar]
  3. Gallo R. C., Mann D., Broder S., Ruscetti F. W., Maeda M., Kalyanaraman V. S., Robert-Guroff M., Reitz M. S., Jr Human T-cell leukemia-lymphoma virus (HTLV) is in T but not B lymphocytes from a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5680–5683. doi: 10.1073/pnas.79.18.5680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gootenberg J. E., Ruscetti F. W., Mier J. W., Gazdar A., Gallo R. C. Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor. J Exp Med. 1981 Nov 1;154(5):1403–1418. doi: 10.1084/jem.154.5.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Haynes B. F., Miller S. E., Palker T. J., Moore J. O., Dunn P. H., Bolognesi D. P., Metzgar R. S. Identification of human T cell leukemia virus in a Japanese patient with adult T cell leukemia and cutaneous lymphomatous vasculitis. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2054–2058. doi: 10.1073/pnas.80.7.2054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kalyanaraman V. S., Sarngadharan M. G., Nakao Y., Ito Y., Aoki T., Gallo R. C. Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1653–1657. doi: 10.1073/pnas.79.5.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kalyanaraman V. S., Sarngadharan M. G., Poiesz B., Ruscetti F. W., Gallo R. C. Immunological properties of a type C retrovirus isolated from cultured human T-lymphoma cells and comparison to other mammalian retroviruses. J Virol. 1981 Jun;38(3):906–915. doi: 10.1128/jvi.38.3.906-915.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kalyanaraman V. S., Sarngadharan M. G., Robert-Guroff M., Miyoshi I., Golde D., Gallo R. C. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science. 1982 Nov 5;218(4572):571–573. doi: 10.1126/science.6981847. [DOI] [PubMed] [Google Scholar]
  9. Kramarsky B., Sarkar N. H., Moore D. H. Ultrastructural comparison of a virus from a Rhesus-monkey mammary carcinoma with four oncogenic RNA viruses. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1603–1607. doi: 10.1073/pnas.68.7.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leonard W. J., Depper J. M., Uchiyama T., Smith K. A., Waldmann T. A., Greene W. C. A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982 Nov 18;300(5889):267–269. doi: 10.1038/300267a0. [DOI] [PubMed] [Google Scholar]
  11. Manzari V., Gallo R. C., Franchini G., Westin E., Ceccherini-Nelli L., Popovic M., Wong-Staal F. Abundant transcription of a cellular gene in T cells infected with human T-cell leukemia-lymphoma virus. Proc Natl Acad Sci U S A. 1983 Jan;80(1):11–15. doi: 10.1073/pnas.80.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Metzgar R. S., Bertoglio J., Anderson J. K., Bonnard G. D., Ruscetti F. W. Detection of HLA-DRw (Ia-like) antigens on human T lymphocytes grown in tissue culture. J Immunol. 1979 Mar;122(3):949–953. [PubMed] [Google Scholar]
  13. Mier J. W., Gallo R. C. Purification and some characteristics of human T-cell growth factor from phytohemagglutinin-stimulated lymphocyte-conditioned media. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6134–6138. doi: 10.1073/pnas.77.10.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miyoshi I., Kubonishi I., Yoshimoto S., Akagi T., Ohtsuki Y., Shiraishi Y., Nagata K., Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
  15. Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  16. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Poiesz B. J., Ruscetti F. W., Mier J. W., Woods A. M., Gallo R. C. T-cell lines established from human T-lymphocytic neoplasias by direct response to T-cell growth factor. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6815–6819. doi: 10.1073/pnas.77.11.6815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pontén J. The relationship between in vitro transformation and tumor formation in vivo. Biochim Biophys Acta. 1976 Dec 23;458(4):397–422. doi: 10.1016/0304-419x(76)90009-3. [DOI] [PubMed] [Google Scholar]
  19. Popovic M., Reitz M. S., Jr, Sarngadharan M. G., Robert-Guroff M., Kalyanaraman V. S., Nakao Y., Miyoshi I., Minowada J., Yoshida M., Ito Y. The virus of Japanese adult T-cell leukaemia is a member of the human T-cell leukaemia virus group. Nature. 1982 Nov 4;300(5887):63–66. doi: 10.1038/300063a0. [DOI] [PubMed] [Google Scholar]
  20. Popovic M., Sarin P. S., Robert-Gurroff M., Kalyanaraman V. S., Mann D., Minowada J., Gallo R. C. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. doi: 10.1126/science.6600519. [DOI] [PubMed] [Google Scholar]
  21. Reitz M. S., Jr, Poiesz B. J., Ruscetti F. W., Gallo R. C. Characterization and distribution of nucleic acid sequences of a novel type C retrovirus isolated from neoplastic human T lymphocytes. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1887–1891. doi: 10.1073/pnas.78.3.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Robert-Guroff M., Nakao Y., Notake K., Ito Y., Sliski A., Gallo R. C. Natural antibodies to human retrovirus HTLV in a cluster of Japanese patients with adult T cell leukemia. Science. 1982 Feb 19;215(4535):975–978. doi: 10.1126/science.6760397. [DOI] [PubMed] [Google Scholar]
  23. Robert-Guroff M., Ruscetti F. W., Posner L. E., Poiesz B. J., Gallo R. C. Detection of the human T cell lymphoma virus p19 in cells of some patients with cutaneous T cell lymphoma and leukemia using a monoclonal antibody. J Exp Med. 1981 Dec 1;154(6):1957–1964. doi: 10.1084/jem.154.6.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ruscetti F. W., Mier J. W., Gallo R. C. Human T-cell growth factor: parameters for production. J Supramol Struct. 1980;13(2):229–241. doi: 10.1002/jss.400130211. [DOI] [PubMed] [Google Scholar]
  25. Yamamoto N., Okada M., Koyanagi Y., Kannagi M., Hinuma Y. Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. Science. 1982 Aug 20;217(4561):737–739. doi: 10.1126/science.6980467. [DOI] [PubMed] [Google Scholar]
  26. Yokoi T., Miyawaki T., Yachie A., Ohzeki S., Taniguchi N. Discrepancy in expression ability of Tac antigen and Ia determinants defined by monoclonal antibodies on activated or cultured cord blood T lymphocytes. J Immunol. 1982 Oct;129(4):1441–1445. [PubMed] [Google Scholar]
  27. Yoshida M., Miyoshi I., Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. doi: 10.1073/pnas.79.6.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES