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The journal of immunology : official journal of the American Association of Immunologists v.198 no.3, 2017년, pp.1210 - 1219   SCI SCIE
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HTLV-1 Tax-Specific CTL Epitope–Pulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with Immune Tolerance against Tax

Ando, Satomi (Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan ); Hasegawa, Atsuhiko (Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan ); Murakami, Yuji (Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan ); Zeng, Na (Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan ); Takatsuka, Natsuko (Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan ); Maeda, Yasuhiro (Department of Hematology, Osaka Minami Medical Center, Osaka 586-8521, Japan ); Masuda, Takao (and ); Suehiro, Youko (Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan ); Kannagi, Mari (Department of Cell Therapy, National Kyushu Cancer Center, Fukuoka 811-1395, Japan );
  • 초록  

    Adult T cell leukemia/lymphoma (ATL), a CD4 + T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1–specific CTL responses may be involved in the elevation of PVL. Our previous animal studies indicated that oral HTLV-1 infection, the major route of infection, caused persistent infection with higher PVL in rats compared with other routes. In this study, we found that Tax-specific CD8 + T cells were present, but not functional, in orally infected rats as observed in some human asymptomatic carriers. Even in the infected rats with immune unresponsiveness against Tax, Tax-specific CTL epitope–pulsed dendritic cell (DC) therapy reduced the PVL and induced Tax-specific CD8 + T cells capable of proliferating and producing IFN-γ. Furthermore, we found that monocyte-derived DCs from most infected individuals still had the capacity to stimulate CMV-specific autologous CTLs in vitro, indicating that DC therapy may be applicable to most infected individuals. These data suggest that peptide-pulsed DC immunotherapy will be useful to induce functional HTLV-1–specific CTLs and decrease PVL in infected individuals with high PVL and impaired HTLV-1–specific CTL responses, thereby reducing the risk of the development of ATL.


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