Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

Oncogene volume 21, pages 2466–2475 (2002)Cite this article

Abstract

The intermediate state of HTLV-1 infection, often found in individuals dually infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the effects of S. stercoralis superinfection on the natural history of HTLV-1 infection, we characterized peripheral blood samples of these individuals in Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied effects of the parasite antigen on T-cells. The dually infected individuals showed a significantly higher provirus load and an increase in CD4+25+ T cell population, with a significant, positive correlation. This increase was attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by inverse-long PCR analysis of the integration sites. S. stercoralis antigen activated the IL-2 promoter in reporter gene assays, induced production of IL-2 by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized by HTLV-1 infection or the transduction of Tax. Taken collectively, these results indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1-infected cells by activating the IL-2/IL-2R system in dually infected carriers, an event which may be a precipitating factor for ATL and inflammatory diseases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Akagi T, Ono H, Shimotohno K . 1995 Blood 86: 4243–4249

  • Arakaki T, Hasegawa H, Asato R, Ikeshiro T, Kinjo F, Saito A, Iwanaga M . 1988 Jpn. J. Trop. Med. Hyg. 16: 11–17

  • Blank A, Yamaguchi K, Blank M, Zaninovic V, Sonoda S, Takatsuki K . 1993 Leuk. Lymph. 9: 407–412

  • Cross SL, Feinberg M, Wolf JB, Holbrook NJ, Wong-Staal F, Leonard WJ . 1987 Cell 49: 47–56

  • Etoh K, Tamiya S, Yamaguchi K, Okayama A, Tsubouchi H, Ideta T, Mueller N, Takatsuki K, Matsuoka M . 1997 Cancer Res. 57: 4862–4867

  • Fujisawa J, Toita M, Yoshida M . 1989 J. Virol. 63: 3234–3239

  • Fujita K, Tajima K, Tominaga S, Tsukidate S, Nakada K, Imai J, Hinuma Y . 1985 Trop. Med. 27: 203–209

  • Furukawa Y, Fujisawa J, Osame M, Toita M, Sonoda S, Kubota R, Ijichi S, Yoshida M . 1992 Blood 80: 1012–1015

  • Gabet A-S, Mortreux F, Talarmin A, Plumelle Y, Leclercq I, Leroy A, Gessain A, Clity E, Joubert M, Wattel E . 2000 Oncogene 19: 4954–4960

  • Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de The G . 1985 Lancet 2: 407–410

  • Gessain A, Saal F, Gout O, Daniel MT, Flandrin G, de The G, Peries J, Sigaux F . 1990 Blood 75: 428–433

  • Greenberg SJ, Jacobson S, Waldmann TA, McFarlin DE . 1989 J. Infect. Dis. 159: 741–744

  • Grove DI . 1996 Adv. Parasitol. 38: 251–309

  • Hattori T, Uchiyama T, Toibana T, Takatsuki K, Uchino H . 1981 Blood 58: 645–647

  • Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I . 1981 Proc. Natl. Acad. Sci. USA 78: 6476–6480

  • Inoue J, Seiki M, Taniguchi T, Tsuru S, Yoshida M . 1986 EMBO J. 5: 2883–2888

  • Itoyama Y, Minato S, Kira J, Goto I, Sato H, Okochi K, Yamamoto N . 1988 Neurology 38: 816–818

  • Kamihira S, Dateki N, Sugahara K, Yamada Y, Tomonaga M, Maeda T, Tahara M . 2000 Int. J. Hematol. 72: 79–84

  • Kreuzer KA, Lass U, Bohn A, Landt O, Schmidt CA . 1999 Cancer Res. 59: 3171–3174

  • Lam KMC, Syed N, Whittle H, Crawford DH . 1991 Lancet 337: 876–878

  • Langridge WHR, Li BJ, Szalay AA . 1987 Methods Enzymol. 153: 336–350

  • Leung K, Nabel GJ . 1988 Nature 333: 776–778

  • Macchia G, Baldari CT, Massone A, Telford JL . 1990 Mol. Cell. Biol. 10: 2731–2737

  • Maeda M, Shimizu A, Ikuta K, Okamoto H, Kashihara M, Uchiyama T, Honjo T, Yodoi J . 1985 J. Exp. Med. 162: 2169–2174

  • Maruyama M, Shibuya H, Harada H, Hatakeyama M, Seiki M, Fujita T, Inoue J, Yoshida M, Taniguchi T . 1987 Cell 48: 343–350

  • Mesnard JM, Devaux C . 1999 Virology 257: 277–284

  • Mochizuki M, Yamaguchi K, Takatsuki K, Watanabe T, Mon S, Tajima K . 1992a Lancet 339: 1110

  • Mochizuki M, Watanabe T, Yamaguchi K, Tajima K, Yoshimura K, Nakashima S, Shirao M, Araki S, Takatsuki K, Mori S, Miyata N . 1992b J. Infect. Dis. 166: 943–944

  • Mori N, Fujii M, Iwai K, Ikeda S, Yamasaki Y, Hata T, Yamada Y, Tanaka Y, Tomonaga M, Yamamoto N . 2000 Blood 95: 3915–3921

  • Murphy EL, Hanchard B, Figueroa JP, Gibbs WN, Lofters WS, Campbell M, Goedert JJ, Blattner WA . 1989 Int. J. Cancer 43: 250–253

  • Nakada K, Kohakura M, Komoda H, Hinuma Y . 1984 Lancet 1: 633–

  • Nakada K, Yamaguchi K, Furugen S, Nakasone T, Nakasone K, Oshiro Y, Kohakura M, Hinuma Y, Seiki M, Yoshida M, Matutes E, Catovsky D, Ishii T, Takatsuki K . 1987 Int. J. Cancer 40: 145–148

  • Neva FA . 1986 J. Infect. Dis. 153: 397–406

  • Okamoto T, Ohno Y, Tsugane S, Watanabe S, Shimoyama M, Tajima K, Miwa M, Shimotohno K . 1989 Jpn. J. Cancer Res. 80: 191–195

  • Ono A, Mochizuki M, Yamaguchi K, Miyata N, Watanabe T . 1995 Br. J. Ophthalmol. 79: 270–276

  • Ono A, Ikeda E, Mochizuki M, Matsuoka M, Yamaguchi K, Sawada T, Yamane S, Tokudome S, Watanabe T . 1998 Jpn. J. Cancer Res. 89: 608–614

  • Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M . 1986 Lancet 1: 1031–1032

  • Patey O, Gessain A, Breuil J, Courillon-Mallet A, Daniel MT, Miclea JM, Roucayrol AM, Signaux F, Lafaix C . 1992 AIDS 6: 575–579

  • Plumelle Y, Pascaline N, Nguyen D, Panelatti G, Jouannelle A, Jouault H, Imbert M . 1993 Hematol. Pathol. 7: 251–262

  • Sato Y, Takara M, Otsuru M . 1985 Trans. Roy. Soc. Trop. Med. Hyg. 79: 51–55

  • Sato Y, Shiroma Y . 1989 Clin. Immunol. Immunopathol. 53: 430–438

  • Sato Y, Ryumon I . 1990 Jpn. J. Parasitol. 39: 213–219

  • Satoh M, Tsukidate S, Fujita K, Yamamoto K . 1991 Int. Arch. Allergy. Appl. Immunol. 96: 95–96

  • Siekevitz M, Feinberg MB, Holbrook N, Wong-Staal F, Greene WC . 1987 Proc. Natl. Acad. Sci. USA 84: 5389–5393

  • Sugamura K, Fujii M, Kannagi M, Sakitani M, Takeuchi M, Hinuma Y . 1984 Int. J. Cancer 34: 221–228

  • Tajima K, Tominaga S, Suchi T . 1986 Hematol. Oncol. 4: 31–44

  • Tanaka Y, Yoshida A, Takayama Y, Tsujimoto H, Tsujimoto A, Hayami M, Tozawa H . 1990 Jpn. J. Cancer Res. 81: 225–231

  • Taniguchi T, Minami Y . 1993 Cell 73: 5–8

  • Tatewaki M, Yamaguchi K, Matsuoka M, Ishii T, Miyasaka M, Mori S, Takatsuki K, Watanabe T . 1995 Blood 86: 3109–3117

  • Uchiyama T, Hori T, Tsudo M, Wano Y, Umadome H, Tamori S, Yodoi J, Maeda M, Sawami H, Uchino H . 1985 J. Clin. Invest. 76: 446–453

  • Watanabe T, Yamaguchi K, Takatsuki K, Osame M, Yoshida M . 1990 J. Exp. Med. 172: 759–765

  • Watanabe T . 1997 Int. J. Hematol. 66: 257–278

  • Wittwer CT, Herrman MG, Moss AA, Rasmussen RP . 1997 Biotechniques 22: 130–138

  • Yamaguchi K, Matutes E, Catovsky D, Galton DAG, Nakada K, Takatsuki K . 1987 Lancet 2: 94–95

  • Yamaguchi K, Kiyokawa T, Nakada K, Yul LS, Asou N, Ishii T, Sanada I, Seiki M, Yoshida M, Matutes E, Catovsky D, Takatsuki K . 1988 Br. J. Haematol. 68: 169–174

  • Yoshida M, Miyoshi I, Hinuma Y . 1982 Proc. Natl. Acad. Sci. USA 79: 2031–2035

  • Yoshida M, Seiki M, Yamaguchi K, Takatsuki K . 1984 Proc. Natl. Acad. Sci. USA 81: 2534–2537

  • Yoshida M, Osame M, Kawai H, Toita M, Kuwasaki N, Nishida Y, Hiraki Y, Takahashi K, Nomura K, Sonoda S . 1989 Ann. Neurol. 26: 331–335

  • Yoshimura K, Mochizuki M, Araki S, Miyata N, Yamaguchi K, Tajima K, Watanabe T . 1993 Am. J. Ophthalmol. 116: 156–163

Download references

Acknowledgements

We thank Drs G Macchia, Sclavo Research Center and K Leung, University of Michigan, for donating IL-2-CAT and IL-2R-CAT, respectively, and Drs M Maeda, Kyoto University, T Akagi, Osaka Biomedical Institute and K Sugamura for donating Sez, Tax1-B and TL-OM1 cell lines, respectively. We also thank M Ohara for comments on the manuscript. This work was supported in part by Grant-in-Aid for Cancer Research for T Watanabe (06280117) and Grant-in-Aid for Scientific Research to Y Sato (08670284) from the Ministry of Education, Science, Technology, Sports and Culture of Japan.

Author information

Authors and Affiliations

  1. Division of Pathology, Institute of Medical Science, University of Tokyo, Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Masao Satoh & Toshiki Watanabe

  2. Department of Medical Zoology, Saitama Medical School, Saitama, Japan

    Masao Satoh & Eitaro Hori

  3. Department of Parasitology, School of Medicine, University of the Ryukyu, Okinawa, Japan

    Hiromu Toma & Yoshiya Sato

  4. Department of Laboratory Medicine, Nagasaki University School of Medicine, Nagasaki, Japan

    Kazuyuki Sugahara & Shimeru Kamihira

  5. Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan

    Ken-ichiro Etoh

  6. Izumizaki Hospital, Okinawa, Japan

    Yoshiyuki Shiroma & Susumu Kiyuna

  7. Gushikawa Clinic, Okinawa, Japan

    Masahiro Takara

  8. Institute for Virus Research, Kyoto University, Kyoto, Japan

    Masao Matsuoka

  9. Blood Transfusion Service, School of Medicine, Kumamoto University, Kumamoto, 860-8556, Japan

    Kazunari Yamaguchi

  10. Okinawa Kyodo Hospital, Okinawa, Japan

    Kiyonobu Nakada

  11. Department of Medical Zoology, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Koichiro Fujita

  12. Department of Parasitology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Somei Kojima

  13. Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

    Yuetsu Tanaka

Authors
  1. Masao Satoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiromu Toma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuyuki Sugahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ken-ichiro Etoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshiyuki Shiroma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Susumu Kiyuna
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masahiro Takara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masao Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazunari Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kiyonobu Nakada
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Koichiro Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Somei Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Eitaro Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yuetsu Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Shimeru Kamihira
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yoshiya Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Toshiki Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshiki Watanabe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Satoh, M., Toma, H., Sugahara, K. et al. Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis. Oncogene 21, 2466–2475 (2002). https://doi.org/10.1038/sj.onc.1205329

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205329

Keywords

This article is cited by

Search

Advanced search

Quick links