title: 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.
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.
authors.affiliation: Division of Pathology, Institute of Medical Science, University of Tokyo, Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Satoh
authors.forename: Hiromu
authors.initials: H
authors.lastname: Toma
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Etoh
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shiroma
authors.forename: Susumu
authors.initials: S
authors.lastname: Kiyuna
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takara
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kiyonobu
authors.initials: K
authors.lastname: Nakada
authors.forename: Koichiro
authors.initials: K
authors.lastname: Fujita
authors.forename: Somei
authors.initials: S
authors.lastname: Kojima
authors.forename: Eitaro
authors.initials: E
authors.lastname: Hori
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshiki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002353:Carrier State; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D005260:Female; D015490:HTLV-I Infections / Q000276:immunology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000302:isolation & purification; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000502:physiology; D017171:Strongyloides stercoralis / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000145:classification; D019562:Viral Load
chemical_list: D000947:Antigens, Helminth; D007376:Interleukin-2; D015375:Receptors, Interleukin-2