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. 2002 Apr 11;21(16):2466-75. doi: 10.1038/sj.onc.1205329.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Carrier State
  • Cell Line
  • Cells, Cultured
  • Clone Cells
  • Female
  • HTLV-I Infections / immunology
  • HTLV-I Infections / virology
  • Human T-lymphotropic virus 1 / isolation & purification*
  • Humans
  • Immunophenotyping
  • Interleukin-2 / physiology*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Proviruses / isolation & purification
  • Receptors, Interleukin-2 / analysis
  • Receptors, Interleukin-2 / physiology
  • Strongyloides stercoralis / immunology*
  • Strongyloidiasis / immunology*
  • T-Lymphocyte Subsets / classification
  • Viral Load


  • Antigens, Helminth
  • Interleukin-2
  • Receptors, Interleukin-2