Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1995 Apr 1;181(4):1575–1580. doi: 10.1084/jem.181.4.1575

Human T lymphocyte virus 1 from a leukemogenic cell line mediates in vivo and in vitro lymphocyte apoptosis

PMCID: PMC2191945  PMID: 7699338

Abstract

HTLV-1 is implicated in the development of diverse diseases. However, most HTLV-1-infected individuals remain asymptomatic. How HTLV-1 infection leads to disparate consequences remains a mystery, despite extensive investigation of HTLV-1 isolates from infected individuals. As in human infection, experimental HTLV-1 infection in rabbits is generally benign, although HTLV-1-infected rabbit T cell lines that mediate lethal leukemia-like disease have been reported. We report here that thymuses from mature outbred rabbits inoculated with a lethal leukemia-like disease have been reported. We report here that thymuses from mature outbred rabbits inoculated with a lethal HTLV-1 T cell line (RH/K34) showed morphological and biochemical evidence of apoptosis, whereas thymuses from rabbits inoculated with nonlethal HTLV-1 T cell lines showed no signs of apoptosis. Exposure of rabbit or human lymphocytes to purified virus from RH/K34 caused rapid induction of apoptosis, providing an in vitro correlate to the pathogenic effects. By contrast, virus isolated from a nonlethal cell line mediated dose- dependent lymphocyte proliferation. These data implicate lymphocyte apoptosis as a potential mechanism by which the lethal HTLV-1 cell line causes fulminant disease and provide a means to identify factors contributing to HTLV-1 disease. Results from this HTLV-1 infection model can provide insight into variations in HTLV-1 pathogenicity in human infection.

Full Text

The Full Text of this article is available as a PDF (736.4 KB).

Selected References

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

  1. Arthur L. O., Bess J. W., Jr, Sowder R. C., 2nd, Benveniste R. E., Mann D. L., Chermann J. C., Henderson L. E. Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines. Science. 1992 Dec 18;258(5090):1935–1938. doi: 10.1126/science.1470916. [DOI] [PubMed] [Google Scholar]
  2. Banda N. K., Bernier J., Kurahara D. K., Kurrle R., Haigwood N., Sekaly R. P., Finkel T. H. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J Exp Med. 1992 Oct 1;176(4):1099–1106. doi: 10.1084/jem.176.4.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bonyhadi M. L., Rabin L., Salimi S., Brown D. A., Kosek J., McCune J. M., Kaneshima H. HIV induces thymus depletion in vivo. Nature. 1993 Jun 24;363(6431):728–732. doi: 10.1038/363728a0. [DOI] [PubMed] [Google Scholar]
  4. Cohen D. I., Tani Y., Tian H., Boone E., Samelson L. E., Lane H. C. Participation of tyrosine phosphorylation in the cytopathic effect of human immunodeficiency virus-1. Science. 1992 Apr 24;256(5056):542–545. doi: 10.1126/science.1570514. [DOI] [PubMed] [Google Scholar]
  5. Cohen J. J., Duke R. C., Fadok V. A., Sellins K. S. Apoptosis and programmed cell death in immunity. Annu Rev Immunol. 1992;10:267–293. doi: 10.1146/annurev.iy.10.040192.001411. [DOI] [PubMed] [Google Scholar]
  6. Debatin K. M., Goldman C. K., Waldmann T. A., Krammer P. H. APO-1-induced apoptosis of leukemia cells from patients with adult T-cell leukemia. Blood. 1993 Jun 1;81(11):2972–2977. [PubMed] [Google Scholar]
  7. Evangelista A., Maroushek S., Minnigan H., Larson A., Retzel E., Haase A., Gonzalez-Dunia D., McFarlin D., Mingioli E., Jacobson S. Nucleotide sequence analysis of a provirus derived from an individual with tropical spastic paraparesis. Microb Pathog. 1990 Apr;8(4):259–278. doi: 10.1016/0882-4010(90)90052-r. [DOI] [PubMed] [Google Scholar]
  8. Gazzolo L., Duc Dodon M. Direct activation of resting T lymphocytes by human T-lymphotropic virus type I. Nature. 1987 Apr 16;326(6114):714–717. doi: 10.1038/326714a0. [DOI] [PubMed] [Google Scholar]
  9. Gessain A., Barin F., Vernant J. C., Gout O., Maurs L., Calender A., de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  10. Gray G. S., White M., Bartman T., Mann D. Envelope gene sequence of HTLV-1 isolate MT-2 and its comparison with other HTLV-1 isolates. Virology. 1990 Jul;177(1):391–395. doi: 10.1016/0042-6822(90)90498-g. [DOI] [PubMed] [Google Scholar]
  11. Groux H., Torpier G., Monté D., Mouton Y., Capron A., Ameisen J. C. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med. 1992 Feb 1;175(2):331–340. doi: 10.1084/jem.175.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hanaoka M., Sasaki M., Matsumoto H., Tankawa H., Yamabe H., Tomimoto K., Tasaka C., Fujiwara H., Uchiyama T., Takatsuki K. Adult T cell leukemia. Histological classification and characteristics. Acta Pathol Jpn. 1979 Sep;29(5):723–738. doi: 10.1111/j.1440-1827.1979.tb00940.x. [DOI] [PubMed] [Google Scholar]
  13. Jeurissen S. H., Wagenaar F., Pol J. M., van der Eb A. J., Noteborn M. H. Chicken anemia virus causes apoptosis of thymocytes after in vivo infection and of cell lines after in vitro infection. J Virol. 1992 Dec;66(12):7383–7388. doi: 10.1128/jvi.66.12.7383-7388.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kimata J. T., Palker T. J., Ratner L. The mitogenic activity of human T-cell leukemia virus type I is T-cell associated and requires the CD2/LFA-3 activation pathway. J Virol. 1993 Jun;67(6):3134–3141. doi: 10.1128/jvi.67.6.3134-3141.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Komurian F., Pelloquin F., de Thé G. In vivo genomic variability of human T-cell leukemia virus type I depends more upon geography than upon pathologies. J Virol. 1991 Jul;65(7):3770–3778. doi: 10.1128/jvi.65.7.3770-3778.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laurent-Crawford A. G., Krust B., Rivière Y., Desgranges C., Muller S., Kieny M. P., Dauguet C., Hovanessian A. G. Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells. AIDS Res Hum Retroviruses. 1993 Aug;9(8):761–773. doi: 10.1089/aid.1993.9.761. [DOI] [PubMed] [Google Scholar]
  17. Maguer V., Cassé-Ripoll H., Gazzolo L., Dodon M. D. Human T-cell leukemia virus type I-induced proliferation of human immature CD2+CD3- thymocytes. J Virol. 1993 Sep;67(9):5529–5537. doi: 10.1128/jvi.67.9.5529-5537.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Malik K. T., Even J., Karpas A. Molecular cloning and complete nucleotide sequence of an adult T cell leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate of Caribbean origin: relationship to other members of the ATLV/HTLV-I subgroup. J Gen Virol. 1988 Jul;69(Pt 7):1695–1710. doi: 10.1099/0022-1317-69-7-1695. [DOI] [PubMed] [Google Scholar]
  19. Miyoshi I., Yoshimoto S., Kubonishi I., Fujishita M., Ohtsuki Y., Yamashita M., Yamato K., Hirose S., Taguchi H., Niiya K. Infectious transmission of human T-cell leukemia virus to rabbits. Int J Cancer. 1985 Jan 15;35(1):81–85. doi: 10.1002/ijc.2910350113. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Punt J. A., Osborne B. A., Takahama Y., Sharrow S. O., Singer A. Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28. J Exp Med. 1994 Feb 1;179(2):709–713. doi: 10.1084/jem.179.2.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rojko J. L., Fulton R. M., Rezanka L. J., Williams L. L., Copelan E., Cheney C. M., Reichel G. S., Neil J. C., Mathes L. E., Fisher T. G. Lymphocytotoxic strains of feline leukemia virus induce apoptosis in feline T4-thymic lymphoma cells. Lab Invest. 1992 Apr;66(4):418–426. [PubMed] [Google Scholar]
  23. Sawasdikosol S., Hague B. F., Zhao T. M., Bowers F. S., Simpson R. M., Robinson M., Kindt T. J. Selection of rabbit CD4- CD8- T cell receptor-gamma/delta cells by in vitro transformation with human T lymphotropic virus-I. J Exp Med. 1993 Oct 1;178(4):1337–1345. doi: 10.1084/jem.178.4.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schwartz L. M., Osborne B. A. Programmed cell death, apoptosis and killer genes. Immunol Today. 1993 Dec;14(12):582–590. doi: 10.1016/0167-5699(93)90197-S. [DOI] [PubMed] [Google Scholar]
  25. Seto A., Kawanishi M., Matsuda S., Ogawa K., Miyoshi I. Adult T cell leukemia-like disease experimentally induced in rabbits. Jpn J Cancer Res. 1988 Mar;79(3):335–341. doi: 10.1111/j.1349-7006.1988.tb01596.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Seto A., Kawanishi M., Matsuda S., Ogawa K. Seronegative virus carriers in the infection of rabbits with human T lymphotropic virus type I. J Exp Med. 1988 Dec 1;168(6):2409–2414. doi: 10.1084/jem.168.6.2409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shi Y. F., Bissonnette R. P., Parfrey N., Szalay M., Kubo R. T., Green D. R. In vivo administration of monoclonal antibodies to the CD3 T cell receptor complex induces cell death (apoptosis) in immature thymocytes. J Immunol. 1991 May 15;146(10):3340–3346. [PubMed] [Google Scholar]
  28. Tsuda H., Huang R. W., Takatsuki K. Interleukin-2 prevents programmed cell death in adult T-cell leukemia cells. Jpn J Cancer Res. 1993 Apr;84(4):431–437. doi: 10.1111/j.1349-7006.1993.tb00154.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wucherpfennig K. W., Höllsberg P., Richardson J. H., Benjamin D., Hafler D. A. T-cell activation by autologous human T-cell leukemia virus type I-infected T-cell clones. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2110–2114. doi: 10.1073/pnas.89.6.2110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Zhao T. M., Robinson M. A., Sawasdikosol S., Simpson R. M., Kindt T. J. Variation in HTLV-I sequences from rabbit cell lines with diverse in vivo effects. Virology. 1993 Jul;195(1):271–274. doi: 10.1006/viro.1993.1373. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES