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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
. 1982 Mar;79(5):1653–1657. doi: 10.1073/pnas.79.5.1653

Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan

V S Kalyanaraman *, M G Sarngadharan , Y Nakao , Y Ito §, T Aoki , R C Gallo †,
PMCID: PMC346034  PMID: 6951204

Abstract

In Japan, adult T-cell leukemias and lymphomas are more common than in the United States and Europe, and in the southwest part of Japan these T-cell malignancy cases appear in clusters. Therefore, we investigated the involvement in these leukemias and lymphomas of the human T-cell leukemia virus (HTLV) that was previously isolated in one of our laboratories from cultured T cells of some patients in the United States with leukemias and lymphomas involving relatively mature T cells. High titers of antibodies capable of quantitative precipitation of 125I-labeled p24, a well characterized core protein of HTLV, were detected in 12 of 12 patients with untreated adult T-cell leukemia (ATL). (One negative was a patient on chemotherapy.) Ten of the 12 positive samples were from an area where the disease is endemic. Strong precipitating antibodies were also detected in five of seven cases of T-cell malignant lymphoma (TML) which differs from ATL by having fewer leukemic cells in the peripheral blood. High antibody titers were also observed in one of five cases of acute monoblastic leukemia and one of eight cases of chronic myelogenous leukemia in the blast phase of the disease. Low to moderate titers of antibodies were detected in several categories of leukemia (two cases of blast-phase chronic myelogenous leukemia, two cases of acute lymphoblastic leukemia of the null-cell type, and one case of acute myelogenous leukemia). Among all categories of leukemias, except ATL and TML, more cases were negative than positive for anti-p24 activity. All of 79 sera from normal Japanese, including 39 collected from the endemic ATL area of southwest Japan, were negative for antibodies to HTLV p24. All the positive reactivities observed were highly specific to HTLV. The only competition observed in the precipitation of HTLV p24 was with HTLV or with cell lines expressing HTLV and not with various animal retroviruses or a large number of human and subhuman primate cell lines, not known to be producing HTLV. The data strongly indicate an association of HTLV with the increased incidence of ATL in parts of Japan, probably with other forms of leukemias in Japan, and, less commonly, with certain T-cell malignancies in the United States.

Keywords: RNA tumor virus, type C virus, radioimmunoassays, Japanese adult T-cell leukemia, T-cell malignant lymphoma

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Selected References

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  1. Barbacid M., Bolognesi D., Aaronson S. A. Humans have antibodies capable of recognizing oncoviral glycoproteins: demonstration that these antibodies are formed in response to cellular modification of glycoproteins rather than as consequence of exposure to virus. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1617–1621. doi: 10.1073/pnas.77.3.1617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Jarrett W., Jarrett O., Mackey L., Laird H., Hardy W., Jr, Essex M. Horizontal transmission of leukemia virus and leukemia in the cat. J Natl Cancer Inst. 1973 Sep;51(3):833–841. doi: 10.1093/jnci/51.3.833. [DOI] [PubMed] [Google Scholar]
  5. Kalyanaraman V. S., Sarngadharan M. G., Bunn P. A., Minna J. D., Gallo R. C. Antibodies in human sera reactive against an internal structural protein of human T-cell lymphoma virus. Nature. 1981 Nov 19;294(5838):271–273. doi: 10.1038/294271a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Lukes R. J., Collins R. D. Lukes-Collins classification and its significance. Cancer Treat Rep. 1977 Sep;61(6):971–979. [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Oroszlan S., Sarngadharan M. G., Copeland T. D., Kalyanaraman V. S., Gilden R. V., Gallo R. C. Primary structure analysis of the major internal protein p24 of human type C T-cell leukemia virus. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1291–1294. doi: 10.1073/pnas.79.4.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Poiesz B. J., Ruscetti F. W., Reitz M. S., Kalyanaraman V. S., Gallo R. C. Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sézary T-cell leukaemia. Nature. 1981 Nov 19;294(5838):268–271. doi: 10.1038/294268a0. [DOI] [PubMed] [Google Scholar]
  14. Posner L. E., Robert-Guroff M., Kalyanaraman V. S., Poiesz B. J., Ruscetti F. W., Fossieck B., Bunn P. A., Jr, Minna J. D., Gallo R. C. Natural antibodies to the human T cell lymphoma virus in patients with cutaneous T cell lymphomas. J Exp Med. 1981 Aug 1;154(2):333–346. doi: 10.1084/jem.154.2.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Rho H. M., Poiesz B., Ruscetti F. W., Gallo R. C. Characterization of the reverse transcriptase from a new retrovirus (HTLV) produced by a human cutaneous T-cell lymphoma cell line. Virology. 1981 Jul 15;112(1):355–360. doi: 10.1016/0042-6822(81)90642-5. [DOI] [PubMed] [Google Scholar]
  17. Ruscetti F. W., Morgan D. A., Gallo R. C. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol. 1977 Jul;119(1):131–138. [PubMed] [Google Scholar]
  18. Sarin P. S., Anderson P. N., Gallo R. C. Terminal deoxynucleotidyl transferase activities in human blood leukocytes and lymphoblast cell lines: high levels in lymphoblast cell lines and in blast cells of some patients with chronic myelogenous leukemia in acute phase. Blood. 1976 Jan;47(1):11–20. [PubMed] [Google Scholar]
  19. Shamoto M., Murakami S., Zenke T. Adult T-cell leukemia in Japan: an ultrastructural study. Cancer. 1981 Apr 1;47(7):1804–1811. doi: 10.1002/1097-0142(19810401)47:7<1804::aid-cncr2820470714>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  20. Snyder H. W., Jr, Fleissner E. Specificity of human antibodies to oncovirus glycoproteins: recognition of antigen by natural antibodies directed against carbohydrate structures. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1622–1626. doi: 10.1073/pnas.77.3.1622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Uchiyama T., Yodoi J., Sagawa K., Takatsuki K., Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481–492. [PubMed] [Google Scholar]

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