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.
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.
Satoh
Masao
M
Division of Pathology, Institute of Medical Science, University of Tokyo, Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Toma
Hiromu
H
Sugahara
Kazuyuki
K
Etoh
Ken-ichiro
K
Shiroma
Yoshiyuki
Y
Kiyuna
Susumu
S
Takara
Masahiro
M
Matsuoka
Masao
M
Yamaguchi
Kazunari
K
Nakada
Kiyonobu
K
Fujita
Koichiro
K
Kojima
Somei
S
Hori
Eitaro
E
Tanaka
Yuetsu
Y
Kamihira
Shimeru
S
Sato
Yoshiya
Y
Watanabe
Toshiki
T
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
D000947:Antigens, Helminth; D007376:Interleukin-2; D015375:Receptors, Interleukin-2