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