HTLV-1-specific T cell suppression in infected individuals

• Project/Area Number: 23591414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HASEGAWA Atsuhiko 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (90508334)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: immunosuppression / CTL / ATL / HTLV-1 / 成人T細胞白血病 / HTLV-1特異的T細胞 / 免疫抑制 / Tax特異的T細胞 / Tax特異的T細胞応答

Research Abstract

It is believed that a weak CD8+ T cell response specific for human T-cell leukemia virus type 1 (HTLV-1) may be one of risk factors for the development of adult T-cell leukemia (ATL). In this study, we showed that a low HTLV-1-specific CD8+ T cell response could be observed not only in most ATL patients but also in a small population of asymptomatic carriers. We also found that this low CD8+ T cell response might be attributed mainly to functional impairment of HTLV-1-specific CD8+ T cells themselves and in part to a reduced function of antigen-presenting cells and an immune suppression by regulatory T cells and infected cells.

Research Products

• [Journal Article] Interferon-α(IFN-α) suppresses HTLV-1 gene expression and cell cycling, while IFN-αcombined with zidovudin induces p53 signaling and apoptosis in HTLV-1-infected cells (2013)
  • Author(s): Kinpara S, Kijiyama M, Takamori A, Hasegawa A, Sasada A, Masuda T, Tanaka Y, Utsunomiya A, Kannagi M
  • Journal Title: Retrovirology Volume: 10 Issue: 1 Pages: 52-52
  • DOI: 10.1186/1742-4690-10-52
  • Peer Reviewed
• [Journal Article] Potential contribution of a novel Taxepitope-specific CD4+ T cells tograftversus-Tax effects in adult T-cell leukemia patients after allogeneichematopoietic stem celltransplantation. (2013)
  • Author(s): Tamai Y., Hasegawa A., Takamori A., et al.
  • Journal Title: Journal of Immunology Volume: in press Issue: 8 Pages: 4382-4392
  • DOI: 10.4049/jimmunol.1202971
  • Peer Reviewed
• [Journal Article] The role of acquired and innate immunity in human T-cell leukemia virus type 1-mediated diseases (2012)
  • Author(s): Mari Kannagi
  • Journal Title: Frontiers in Microbiology Volume: 3 Pages: 1-10
  • DOI: 10.3389/fmicb.2012.00323
  • Peer Reviewed
• [Journal Article] Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+cytotoxic T lymphocytes in a minor population of asymptomatic human T-cell leukemia virus type 1-carriers. (2011)
  • Author(s): Takamori A., Hasegawa A., Utsunomiya A., et al
  • Journal Title: Retrovirology Volume: 8 Issue: 1 Pages: 100-100
  • DOI: 10.1186/1742-4690-8-100
  • Peer Reviewed
• [Journal Article] Double control systems for human T-cell leukemia virus type 1 by innate and acquired immunity (2011)
  • Author(s): Kannagi M, Hasegawa A, Kinpara S, Shimizu Y, Takamori A, Utsunomiya A
  • Journal Title: Cancer Sci Volume: 102(4) Issue: 4 Pages: 670-6
  • DOI: 10.1111/j.1349-7006.2011.01862.x
  • NAID: 10029291668
  • Peer Reviewed
• [Presentation] ATL発症予防、治療を目的としたペプチドパルス樹状細胞療法に関する研究 (2013)
  • Author(s): 長谷川温彦、安藤聡美、高森絢子、玉井洋太郎、笹田亜麻子、神奈木真理
  • Organizer: 第23回日本樹状細胞研究会
  • Place of Presentation: 京都
  • Year and Date: 2013-05-17
• [Presentation] Peptide-pulsed dendritic cell vaccine reinduced functional Tax-specific CD8+ T cells in orally HTLV-1 infected rats with impaired Tax-specific CD8+ T cells responses (2013)
  • Author(s): Ando S, Hasegawa A, Murakami Y, Masuda T, Kannagi M
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張
• [Presentation] Kinetics of Tax-specific CTL in ATL patients following hematopoietic stem cell transplantation from uninfected donors (2013)
  • Author(s): Takamori A, Hasegawa A, Utsunomiya A, Choi I, Tanosaki R, Eto T, Kato K, Tamai Y, Sasada A, Suehiro Y, Uike N, Kannagi M
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] The phase-I study of a therapeutic vaccine to ATL patients with autologous dendritic cells pulsed with Tax peptides (2013)
  • Author(s): Suehiro Y, Hasegawa A, Iino T, Sasada A, Watanabe N, Tanosaki R, Utsunomiya A, Matsuoka M, Teshima T, Akashi K, Okamura J, Kannagi M, Uike N
  • Organizer: 第72回日本癌学会シンポジウム
  • Place of Presentation: 横浜
• [Presentation] Identification of novel HTLV-1-specific CD4 epitopes in ATL patients after hematopoietic stem cell transplantation (2013)
  • Author(s): Hasegawa A, Tamai Y, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Suehiro Y, Maeda Y, Yamano Y, Uike N, Kannagi M
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] Hasegawa A, Suehiro Y, Takamori A, Kinpara S, Ando S, Utsunomiya A, Choi I, Uike N. Immunological control of HTLV-1: Prospective therapy towards prophylaxis of disease (2013)
  • Author(s): Kannagi M
  • Organizer: 第6回HTLV-1研究会国際シンポジウム
  • Place of Presentation: 東京
• [Presentation] Augmentation of donor-derived Tax-specific CTL responses by a novel Tax epitope-specific CD4+ helper T-cells in ATL patients after allogeneic hematopoietic stem cell transplanation (2013)
  • Author(s): Hasegawa A, Tamai Y, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Maeda Y, Yamano Y, Etoh T, Koh KR, Nakamae H, Suehiro Y, Kato K, Takemoto S, Okamura J, Uike N, Kannagi M
  • Organizer: 16th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Montréal, Canada
• [Presentation] The phase-I study of a therapeutic vaccine to ATL patients with autologous dendritic cells pulsed with peptides corresponding to Tax-specific CTL epitopes (2013)
  • Author(s): Suehiro Y, Hasegawa A, Iino T, Sasada A, Watanabe N, Choi I, Fukuda T, Takaishi S, Tanosaki R, Utsunomiya A, Miura O, Matsuoka M, Teshima T, Akashi K, Okamura J, Kannagi M, Uike N
  • Organizer: 16th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Montréal, Canada
• [Presentation] Unresponsiveness of Tax-specific CTLs in Rats Orally Infected with HTLV-1 and Reinduction of Functional Tax-specific CTLs by Peptide-pulsed BMDC Vaccine (2013)
  • Author(s): Hasegawa A
  • Organizer: 第4回日本血液学会(JSH)国際シンポジウム
  • Place of Presentation: 松山
• [Presentation] Impact of innate and acquired immune responses in Adult T-cell Leukemia (2013)
  • Author(s): Kannagi M, Kinpara S, Takamori A, Sasada A, Hasegawa A
  • Organizer: The 9^<th> AACR-Japanese cancer association joint conference
  • Place of Presentation: Maui, HI
• [Presentation] Identification of a novel HLA-DR1-restricted dominant epitope recognized by HTLV-1 Tax-specific CD4^+ T-cells augmenting HTLV-1-specific CTL expansion in ATL patients after allogeneic HSCT (2013)
  • Author(s): Hasegawa A, Tamai Y, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Maeda Y, Yamano Y, Etoh T, Koh KR, Nakamae H, Suehiro Y, Kato K, Takemoto S, Okamura J, Uike N, Kannagi M
  • Organizer: The 9^<th> AACR-Japanese cancer association joint conference
  • Place of Presentation: Maui, HI
• [Presentation] ATL発症予防、治療を目的としたペプチドパルス樹状細胞療法に関する研究 (2013)
  • Author(s): 長谷川温彦、安藤聡美、高森絢子、玉井洋太郎、笹田亜麻子、神奈木真理.
  • Organizer: 第23回日本樹状細胞研究会
  • Place of Presentation: 国立京都国際会館、京都
• [Presentation] Unresponsiveness of Tax-specific CTLs in Rats Orally Infected with HTLV-1 and Reinduction of Functional Tax-specific CTLs by Peptide-pulsed BMDC Vaccine (2013)
  • Author(s): Hasegawa A
  • Organizer: The 4th Japanese Society of Hematology, International Symposium
  • Place of Presentation: 大和屋本店、松山
• [Presentation] Augmentation of donor-derived Tax-specific CTL responses by a novel Tax epitope-specific CD4+ helper T-cells in ATL patients after allogeneic hematopoietic stem cell transplanation (2013)
  • Author(s): Hasegawa A, Tamai Y, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Maeda Y, Yamano Y, Etoh T, Koh KR, Nakamae H, Suehiro Y, Kato K, Takemoto S, Okamura J, Uike N, Kannagi M.
  • Organizer: The 16th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Montreal, Canada
• [Presentation] Immunological control of HTLV-1: Prospective therapy towards prophylaxis of disease (2013)
  • Author(s): Kannagi M. Hasegawa A, Suehiro Y, Takamori A, Kinpara S, Ando S, Utsunomiya A, Choi I, Uike N.
  • Organizer: 第6回HTLV-1研究会国際シンポジウム
  • Place of Presentation: 東京大学医科学研究所、東京
• [Presentation] Identification of novel HTLV-1-specific CD4 epitopes in ATL patients after hematopoietic stem cell transplantation (2013)
  • Author(s): Hasegawa A, Tamai Y, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Suehiro Y, Maeda Y, Yamano Y, Uike N, Kannagi M.
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] Peptide-pulsed dendritic cell vaccine reinduced functional Tax-specific CD8+ T cells in orally HTLV-1 infected rats with impaired Tax-specific CD8+ T cells responses (2013)
  • Author(s): Ando S, Hasegawa A, Murakami Y, Masuda T, Kannagi M.
  • Organizer: 第42回日本免疫学会
  • Place of Presentation: 幕張メッセ、千葉
• [Presentation] Identification of a novel HLA-DR1-restricted dominant epitope recognized by HTLV-1 Tax-specific CD4+ T-cells augmenting HTLV-1-specific CTL expansion in ATL patients after allogeneic HSCT (2013)
  • Author(s): 1. Hasegawa A, Tamai Y, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Maeda Y, Yamano Y, Etoh T, Koh KR, Nakamae H, Suehiro Y, Kato K, Takemoto S, Okamura J, Uike N, Kannagi M.
  • Organizer: The 9th AACR-Japanese Cancer Association Joint Conference
  • Place of Presentation: Hyatt Regency Maui (Maui, HI)
• [Presentation] Unresponsiveness of dominant Tax-specific CD8+ T cells in rats orally infected with HTLV-1 (2012)
  • Author(s): Ando S, Murakami Y, Hasegawa A, Masuda T, Kannagi M
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] Functional impairment of CD8+ cytotoxic T lymphocytes selective for HTLV-1-specific responses in early stages of adult T-cell leukemia patients (2012)
  • Author(s): Takamori A, Hasegawa A, Utsunomiya A, Maeda Y, Yamano Y, Masuda M, Tamai Y, Sasada A, Choi I, Uike N, Okamura J, Watanabe T, Kannagi M
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] HTLV-1経口感染ラットを用いたペプチドパルス樹状細胞ワクチン評価系作成のための基礎的研究 (2012)
  • Author(s): 安藤聡美、村上悠二、長谷川温彦、増田貴夫、神奈木真理
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] A novel HLA-DR-restricted epitope recognized by Tax-specific CD4+ T cells in ATL patients after allo-HSCT (2012)
  • Author(s): Tamai Y, Hasegawa A, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Etoh T, Koh KR, Suehiro Y, Okamura J, Uike N, Kannagi M
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] HTLV-1感染者におけるTax特異的T細胞応答およびATL発症予防 (2012)
  • Author(s): 長谷川温彦、高森絢子、宇都宮與、前田裕弘、山野嘉久、増田昌人、清水由紀子、玉井洋太郎、笹田亜麻子、崔日承、鵜池直邦、岡村純、渡邉俊樹、神奈木真理
  • Organizer: 第1回ATLシンポジウム(第5回HTLV-1研究会/シンポジウム)
  • Place of Presentation: 東京
• [Presentation] HTLV-1感染者におけるTax特異的T細胞応答およびATL発症予防 (2012)
  • Author(s): 10. 長谷川 温彦、高森 絢子、宇都宮 與、前田 裕弘、山野 嘉久、増田 昌人、清水 由紀子、玉井 洋太郎、笹田 亜麻子、崔 日承、鵜池 直邦、岡村 純、渡邉 俊樹、神奈木 真理.
  • Organizer: 第1回 ATLシンポジウム（第5回 HTLV-1研究会/シンポジウム）
  • Place of Presentation: 東京大学医科学研究所講堂（東京）
  • Invited
• [Presentation] A novel HLA-DR-restricted epitope recognized by Tax-specific CD4+ T cells in ATL patients after allo-HSCT (2012)
  • Author(s): 8. Tamai Y, Hasegawa A, Takamori A, Sasada A, Tanosaki R, Choi I, Utsunomiya A, Etoh T, Koh KR, Suehiro Y, Okamura J, Uike N, Kannagi M.
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌教育文化会館（札幌）
• [Presentation] Functional impairment of Tax-specific but not CMV-specific CTLs in a minor population of asymptomatic carriers (2011)
  • Author(s): Takamori A, Hasegawa A, Utsunomiya A, Maeda Y, Yamano Y, Shimizu Y, Tamai Y, Sasada A, Zeng N, Choi I, Uike N, Okamura J, Watanabe T, Masuda T, Kannagi M
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] Evaluation of peptide-pulsed dendritic cell vaccine using HTLV-1-infected rat model (2011)
  • Author(s): Hasegawa A, Zeng N, Masuda T, Kannagi M
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] Functional impairment of Tax-specific but not CMV-specific CD8+ T cells in a minor population of asymptomatic carriers (2011)
  • Author(s): Hasegawa A, Takamori A, Utsunomiya A, Maeda Y, Yamano Y, Shimizu Y, Tamai Y, Sasada A, Zeng N, Choi I, Uike N, Okamura J, Watanabe T, Masuda T, Kannagi M
  • Organizer: The XXV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases
  • Place of Presentation: 東京
• [Presentation] The evaluation of peptide-pulsed dendritic cell vaccine in HTLV-1-infected rats with weak T cell responses against HTLV-1 (2011)
  • Author(s): Zeng N, Hasegawa A, Shimizu Y, Tamai Y, Takamori A, Sasada A, Kannagi M
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌
• [Presentation] Functional impairment of Tax-specific but not CMV-specific CD8+ T cells in a minor population of asymptomatic carriers (2011)
  • Author(s): Takamori A, Hasegawa A, Utsunomiya A, Maeda Y, Yamano Y, Shimizu Y, Tamai Y, Sasada A, Zeng N, Choi I, Uike N, Okamura J, Watanabe T, Masuda T, Kannagi M
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌
• [Presentation] 成人T細胞白血病リンパ腫(ATLL)に対する樹状細胞免疫療法に向けた、基礎解析と第I相臨床試験コールドラン (2011)
  • Author(s): 笹田亜麻子、長谷川温彦、清水由紀子、末廣陽子、鵜池直邦、豊嶋崇徳、谷憲三朗、森尾友宏、福田哲也、三浦修、宇都宮與、神奈木真理
  • Organizer: 第3回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: 別府
• [Presentation] The role of innate and acquired immune responses on HTLV-1 infection (2011)
  • Author(s): Kannagi M, Kinpara S, Hasegawa A, Takamori A, Shimizu Y, Utsunomiya A
  • Organizer: The 15^<th> International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Leuven, Belgium
• [Presentation] Functional impairment of Tax-specific but not CMV-specific CTLs in a minor population of asymptomatic carriers (2011)
  • Author(s): Hasegawa A, Takamori A, Utsunomiya A, Maeda Y, Yamano Y, Shimizu Y, Tamai Y, Sasada A, Zeng N, Choi I, Uike N, Okamura J, Watanabe T, Masuda T, Kannagi M
  • Organizer: The 15^<th> International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Leuven, Belgium
• [Presentation] Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+ T lymphocytes in a minor population of asymptomatic HTLV-1-carriers (2011)
  • Author(s): Atsuhiko Hasegawa
  • Organizer: The XXV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases
  • Place of Presentation: 東京大学（東京）
• [Presentation] HTLV-1感染キャリアに観察されたTax特異的CTLの機能不全 (2011)
  • Author(s): 高森 絢子
  • Organizer: 第70回 日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Patent(Industrial Property Rights)] HLA-DR1拘束性Tax特異的CD4+T細胞エピトープ (2013)
  • Inventor(s): 玉井洋太郎,長谷川温彦,神奈木真理,田野崎隆二
  • Industrial Property Rights Holder: 玉井洋太郎,長谷川温彦,神奈木真理,田野崎隆二
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-01-09
  • Overseas
• [Patent(Industrial Property Rights)] HLA-DR1拘束性Tax特異的CD4＋T細胞エピトープ (2013)
  • Inventor(s): 玉井 洋太郎、長谷川 温彦、神奈木 真理、田野崎 隆二
  • Industrial Property Rights Holder: 玉井 洋太郎、長谷川 温彦、神奈木 真理、田野崎 隆二
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-01-09