Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Feb;61(2):207–214. doi: 10.1038/bjc.1990.38

Selection of HTLV-I positive clones is prevented by prostaglandin A in infected cord blood cultures.

C D'Onofrio 1, E Alvino 1, E Garaci 1, E Bonmassar 1, M G Santoro 1
PMCID: PMC1971418  PMID: 2310673

Abstract

Type A prostaglandins (PGA1 and 16,16-dimethyl-PGA2-methyl ester) were found to block the proliferation of HTLV-I infected cord blood lymphocytes (CBL) in vitro, thus preventing the clonal immortalisation that is considered as a predisposing condition to HTLV-I positive leukaemia. PGA1 and di-M-PGA2 did not affect the long-term survival of normal non-infected CBL, whereas they suppressed the proliferation of an established cord-blood derived HTLV-I positive cell line, MT-2. As shown by the number of HTLV-I infected p19+ cells, the block of the selection of immortalised, infected clones by PGAs did not appear to be due to an inhibition of early stages of HTLV-I infection. The possibility that the effect of PGAs could be mediated by an action on the immune response was also examined. PGAs regulated the cell-mediated cytotoxic function of CBL to a different extent when normal non-infected or HTLV-I exposed CBL were compared. In fact, PGAs down-regulated the natural killing and macrophage/lymphocyte cytotoxic response of normal CBL, whereas they did not modify the already depressed immune response of CBL challenged with HTLV-I. These results suggest that the protective effect of PGAs against HTLV-I infection in vitro is mostly related to the direct suppression of the clonal expansion of virus-infected cells, rather than to the anti-viral activity or modulation of the cell-mediated immunity.

Full text

PDF
207

Images in this article

Selected References

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

  1. Akagi T., Ohtsuki Y., Takahashi K., Takeda I., Oka T., Miyoshi I. Immortalization of human lymphocytes by co-cultivation with lethally irradiated autologous T-cell lines harbouring human T-cell leukaemia virus-I. J Cancer Res Clin Oncol. 1985;110(1):82–84. doi: 10.1007/BF00402508. [DOI] [PubMed] [Google Scholar]
  2. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  3. D'Onofrio C., Lohmann-Matthes M. L. Chemiluminescence of macrophages depends upon their differentiation stage: dissociation between phagocytosis and oxygen radical release. Immunobiology. 1984 Dec;167(5):414–430. doi: 10.1016/S0171-2985(84)80074-1. [DOI] [PubMed] [Google Scholar]
  4. D'Onofrio C., Paradisi F. In-vitro differentiation of human monocytes into mature macrophages during long-term cultures. Immunobiology. 1983 Feb;164(1):13–22. doi: 10.1016/S0171-2985(83)80013-8. [DOI] [PubMed] [Google Scholar]
  5. D'Onofrio C., Perno C. F., Mazzetti P., Graziani G., Calio' R., Bonmassar E. Depression of early phase of HTLV-I infection in vitro mediated by human beta-interferon. Br J Cancer. 1988 May;57(5):481–488. doi: 10.1038/bjc.1988.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Vecchis L., Graziani G., Macchi B., Grandori C., Pastore S., Popovic M., Gallo R. C., Bonmassar E. Decline of natural cytotoxicity of human lymphocytes following infection with human T-cell leukemia/lymphoma virus (HTLV). Leuk Res. 1985;9(3):349–355. doi: 10.1016/0145-2126(85)90056-6. [DOI] [PubMed] [Google Scholar]
  7. Duesberg P. H. Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res. 1987 Mar 1;47(5):1199–1220. [PubMed] [Google Scholar]
  8. Franchini G., Wong-Staal F., Gallo R. C. Human T-cell leukemia virus (HTLV-I) transcripts in fresh and cultured cells of patients with adult T-cell leukemia. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6207–6211. doi: 10.1073/pnas.81.19.6207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gallo R. C. The human T-cell leukemia/lymphotropic retroviruses (HTLV) family: past, present, and future. Cancer Res. 1985 Sep;45(9 Suppl):4524s–4533s. [PubMed] [Google Scholar]
  10. Graziani G., Pasqualetti D., Lopez M., D'Onofrio C., Testi A. M., Mandelli F., Gallo R. C., Bonmassar E. Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro. Blood. 1987 Apr;69(4):1175–1181. [PubMed] [Google Scholar]
  11. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Karmali R. A., Sarkar N. H., Whittington E., Good R. A. Prostaglandin regulation of murine mammary tumor virus production: a basis for some of the glucocorticoid and prolactin actions on mammary tumor cell cultures. Prostaglandins Leukot Med. 1982 Dec;9(6):641–655. doi: 10.1016/0262-1746(82)90021-x. [DOI] [PubMed] [Google Scholar]
  13. Knudson A. G., Jr Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437–1443. [PubMed] [Google Scholar]
  14. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  15. Manzari V., Gradilone A., Barillari G., Zani M., Collalti E., Pandolfi F., De Rossi G., Liso V., Babbo P., Robert-Guroff M. HTLV-I is endemic in southern Italy: detection of the first infectious cluster in a white population. Int J Cancer. 1985 Nov 15;36(5):557–559. doi: 10.1002/ijc.2910360507. [DOI] [PubMed] [Google Scholar]
  16. Mitsuya H., Matis L. A., Megson M., Bunn P. A., Murray C., Mann D. L., Gallo R. C., Broder S. Generation of an HLA-restricted cytotoxic T cell line reactive against cultured tumor cells from a patient infected with human T cell leukemia/lymphoma virus. J Exp Med. 1983 Sep 1;158(3):994–999. doi: 10.1084/jem.158.3.994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Olsson I. L., Breitman T. R., Gallo R. C. Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3':5'-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor. Cancer Res. 1982 Oct;42(10):3928–3933. [PubMed] [Google Scholar]
  19. 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]
  20. Santoro M. G., Benedetto A., Carruba G., Garaci E., Jaffe B. M. Prostaglandin A compounds as antiviral agents. Science. 1980 Aug 29;209(4460):1032–1034. doi: 10.1126/science.6157190. [DOI] [PubMed] [Google Scholar]
  21. Santoro M. G., Carruba G., Garaci E., Jaffe B. M., Benedetto A. Prostaglandins of the A series inhibit Sendai virus replication in cultured cells. J Gen Virol. 1981 Mar;53(Pt 1):75–83. doi: 10.1099/0022-1317-53-1-75. [DOI] [PubMed] [Google Scholar]
  22. Santoro M. G., Crisari A., Benedetto A., Amici C. Modulation of the growth of a human erythroleukemic cell line (K562) by prostaglandins: antiproliferative action of prostaglandin A. Cancer Res. 1986 Dec;46(12 Pt 1):6073–6077. [PubMed] [Google Scholar]
  23. Santoro M. G., Favalli C., Mastino A., Jaffe B. M., Esteban M., Garaci E. Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus. Arch Virol. 1988;99(1-2):89–100. doi: 10.1007/BF01311026. [DOI] [PubMed] [Google Scholar]
  24. Santoro M. G., Fukushima M., Benedetto A., Amici C. PGJ2, a new antiviral prostaglandin: inhibition of Sendai virus replication and alteration of virus protein synthesis. J Gen Virol. 1987 Apr;68(Pt 4):1153–1158. doi: 10.1099/0022-1317-68-4-1153. [DOI] [PubMed] [Google Scholar]
  25. Suciu-Foca N., Rubinstein P., Popovic M., Gallo R. C., King D. W. Reactivity of HTLV-transformed human T-cell lines to MHC class II antigens. Nature. 1984 Nov 15;312(5991):275–277. doi: 10.1038/312275a0. [DOI] [PubMed] [Google Scholar]
  26. Svec J., Svec P., Halcak L., Thurzo V. Role of natural prostaglandins in the control of murine mammary tumor virus expression. J Cancer Res Clin Oncol. 1982;103(1):55–67. doi: 10.1007/BF00410306. [DOI] [PubMed] [Google Scholar]
  27. Thorn R. M., Henney C. S. Kinetic analysis of target cell destruction by effector T cells. I. Delineation of parameters related to the frequency and lytic efficiency of killer cells. J Immunol. 1976 Dec;117(6):2213–2219. [PubMed] [Google Scholar]
  28. Volkman D. J., Popovic M., Gallo R. C., Fauci A. S. Human T cell leukemia/lymphoma virus-infected antigen-specific T cell clones: indiscriminant helper function and lymphokine production. J Immunol. 1985 Jun;134(6):4237–4243. [PubMed] [Google Scholar]
  29. Wong-Staal F., Gallo R. C. Human T-lymphotropic retroviruses. Nature. 1985 Oct 3;317(6036):395–403. doi: 10.1038/317395a0. [DOI] [PubMed] [Google Scholar]
  30. Yarchoan R., Guo H. G., Reitz M., Jr, Maluish A., Mitsuya H., Broder S. Alterations in cytotoxic and helper T cell function after infection of T cell clones with human T cell leukemia virus, type I. J Clin Invest. 1986 May;77(5):1466–1473. doi: 10.1172/JCI112459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yoshida M. Expression of the HTLV-1 genome and its association with a unique T-cell malignancy. Biochim Biophys Acta. 1987 Jul 8;907(2):145–161. doi: 10.1016/0304-419x(87)90003-5. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES