title: HTLV-1 Tax-Specific CTL Epitope-Pulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with Immune Tolerance against Tax.
abstract: 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.
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Ando
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; hase.impt@tmd.ac.jp.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Na
authors.initials: N
authors.lastname: Zeng
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Takatsuka
authors.affiliation: Department of Hematology, Osaka Minami Medical Center, Osaka 586-8521, Japan; and.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Cell Therapy, National Kyushu Cancer Center, Fukuoka 811-1395, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Suehiro
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Kannagi
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016356:Gene Products, tax / Q000276:immunology*; D015490:HTLV-I Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D011533:Proviruses / Q000302:isolation & purification; D051381:Rats; D011916:Rats, Inbred F344; D014611:Vaccination; D019562:Viral Load
chemical_list: D016356:Gene Products, tax; C514970:tax protein, Human T-lymphotrophic virus 1; D007371:Interferon-gamma