The roles of innate T cells in bacterial infection

• Project/Area Number: 21390130
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kyushu University
• Principal Investigator: YOSHIKAI Yasunobu 九州大学, 生体防御医学研究所, 教授 (90158402)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Hsakata 九州大学, 生体防御医学研究所, 准教授 (20363369) ; SHBATA Kensuke 九州大学, 生体防御医学研究所, 助教 (50529972)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2009: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 感染免疫 / 自然免疫CD4+T細胞 / CD30L / Listeria monocytogenes / IFN-gamma / 感染防禦 / IL-12/IL-15 / 自然免疫T細胞 / CD301 / IL-17 / 炎症性腸疾患 / 腸内細菌 / IL-2 / IL-15 / HY特異性CD8T細胞 / リステリア感染 / キラー活性 / γインターフェロン / 負の選択

Research Abstract

Innate T cells are defined as(1) cells that develop in the thymus under different signal pathways from conventional T cells,(2) cells that express an activated and/or memory T-cell phenotype and exhibit immediate effector functions.(3) cells that includd y6 T cells, memory phenotype(MP) CD44^<hlgh> CD62L^<low> CD4^+ and CD8^+ T cells. Innate y6 T cells already differentiate into interleukin(IL)-li-producing cells within the fetal thymus. HESl plays a role in regulating differentiation of IL-li producing y6 T cells in thymus and" naturally occurring y6 T cells" play a protective role in the lung at very early stage after systemic infection with Mycobacterium bovis BCG. We further found that IL-lsKo mice are highly susceptible to Listeria monocytogenes and bystander proliferation of the innate CD8^+ T cells induced by L. monocytogenes was impaired in the absence of IL-Is. These results suggested that IL-Is plays an important role in the maintenance and functions of innate CD8^+ T cells, which participate in innate host defense mechanisms. We also found that CDsoLKO mice are highly susceptible to L. monocytogenes infection accompanied by a marked decrease in innate MP IFN-y+ CD4+ T cells at an early stage after infection. These findings suggested that a potential role of CDsoL in activation of innate CD4^+ T cells at an early stage after bacterial in fection.

Research Products

• [Journal Article] A protective role of naturally occurring ILliAproducing 76 T cells in the lung at the early stage of systemic candidiasis in mice (2011)
  • Author(s): Dejima T., Shibata K., Yamada H., Hara H., Iwakura Y., Naito S. and Yoshikai Y.
  • Journal Title: Infect. Immun Volume: 79 Pages: 4503-10
• [Journal Article] CD30 ligand is a target for a novel biological therapy against allergic rhinitis (2011)
  • Author(s): Fuchiwaki T., Sun X., Yamada H., Shibata K Muta H., Podack E. R. Kawauchi H and Yoshikai Y
  • Journal Title: Eur. J. Immunol Volume: 41 Pages: 2947-54
• [Journal Article] nnate memory phenotype CD4+ T cells play a role in early protection against infection with Listeria monocytogenes in a CDsoLdependent manner (2011)
  • Author(s): Umeda K., Sun X. Guo Y., Yamada H., Shibata K. and Yoshikai Y
  • Journal Title: Micrbiol. Immunol Volume: 55 Pages: 645-56
• [Journal Article] Matsuguchi T. Functional involvement of DUSPl6, a JNKspecific phosphatase, in the regulation of T helper cell differentiation (2011)
  • Author(s): Musikacharoen T, Bandow K, Kakimoto K, Kusuyama J, Ohnishi T, Yoshikai Y
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 24896-905
• [Journal Article] Notch-Hesl pathway is required for thedevelopment of ILliproducing y8 T cells (2011)
  • Author(s): Shibata K., Yamada H., Sate T., Dejima S., Nakamura M., , Ikawa T., Hara H., Yamasaki S., Kageyama R., Iwakura Y., Kawamoto H., Ton H. and Yoshikai Y.
  • Journal Title: Blood Volume: 118 Pages: 586-93
• [Journal Article] Preferential accumulation of activated Thl cells in the joints of rheumatoid arthritis and osteoarthritis (2011)
  • Author(s): Yamada H., Nakashima Y., Okazaki K., Mawatari T., Fukushi J, Oyamada A., Fujimura K, Iwamoto Y., and Yoshikai Y.
  • Journal Title: J. Rheumatol Volume: 38 Pages: 1569-75
• [Journal Article] IL-li production by 78 T cells is important for the antitumor effect of Mycobacterium bovis bacillus CalmetteGuerin treatment against bladder cancer (2011)
  • Author(s): Takeuchi A., Dejima T., Yamada H., Shibata K., Nakamura R., Eta M., Nakatani T., Naito S., and Yoshikai Y
  • Journal Title: Eur. J. Immunol Volume: 41 Pages: 246-51
• [Journal Article] Notch-Hes1 pathway is required for the development of IL-17-producing Yδ T cells (2011)
  • Author(s): K.Shibata
  • Journal Title: Blood Volume: 118 Issue: 3 Pages: 586-593
  • DOI: 10.1182/blood-2011-02-334995
  • Peer Reviewed
• [Journal Article] CD30 ligand is a target for a novel biological therapy against allergic rhinitis (2011)
  • Author(s): Fuchiwaki T, et al
  • Journal Title: Eur.J.Immunol Volume: 41 Issue: 10 Pages: 2947-2954
  • DOI: 10.1002/eji.201141423
  • Peer Reviewed
• [Journal Article] Innate memory phenotype CD4+ T cells play a role in early protection against infection with Listeria monocytogenes in a CD30L-dependent manner (2011)
  • Author(s): Umeda K., et al
  • Journal Title: Micrbiol.Immunol. Volume: 55 Issue: 9 Pages: 645-656
  • DOI: 10.1111/j.1348-0421.2011.00362.x
  • Peer Reviewed
• [Journal Article] IL-17 production by γδ T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guerin treatment against bladder cancer. (2011)
  • Author(s): Takeuchi A, et al.
  • Journal Title: Eur.J.Immunol. Volume: 41 Pages: 246-251
  • Peer Reviewed
• [Journal Article] Selective control of type I IFN induction by the Rae activator DOCK2 during TLRmediated plasmacytoid dendritic cell activation (2010)
  • Author(s): otoh K., Tanaka Y., Nishikimi A., Nakamura R., Yamada H., Maeda N., Ishikawa T., Hoshino K., Uru no T., Cao Q, Higashi S., Kawaguchi Y, Enjoji M, Takayanagi, R., Kaisho T. Yoshikai, Y. and Fukui Y.
  • Journal Title: J. Exp. Med Volume: 207 Pages: 721-30
• [Journal Article] Interleukin-ls is critical in the pathogenesis of influenza A virusinduced acute lung injury (2010)
  • Author(s): Nakamura R., Maeda N., Shibata K. Yamada H., Kase T. and Yoshikai Y.
  • Journal Title: J. viral Volume: 84 Pages: 5574-82
• [Journal Article] A critical role of CDso ligand in THli differentiation (2010)
  • Author(s): Sun X. Yamada H., Shibata K., Muta H., Tani K., Podack E. R. Iwakura Y., and Yoshikai Y
  • Journal Title: J. Immunol Volume: 185 Pages: 2222-30
• [Journal Article] CDso ligand is a target for a novel biological therapy against colitis associated with Th17 responses (2010)
  • Author(s): Sun X. Yamada H., Shibata K., Muta H., Tani K., Podack E. R. Iwakura Y. and Yoshikai Y.
  • Journal Title: J. Immunol Volume: 185 Pages: 7671-80
• [Journal Article] Susceptibility of human T-cell leukemia virus type Iinfected cells to humanized anti-CDso monoclonal antibodies in vitro and in vive (2010)
  • Author(s): Maeda, N., Muta, H., Oflazoglu, E. and Yoshikai Y.
  • Journal Title: Cancer Sci Volume: 101 Pages: 224-30
• [Journal Article] Dual specificity phosphatasel6 is a negative regulator of INK activity in T cells (2010)
  • Author(s): Tang C., Yamada H., Shibata K., Yoshida S., Wajjwalku W., and Yoshikai Y.
  • Journal Title: Microbiol. Immunol Volume: 54 Pages: 105-11
• [Journal Article] A critical role of CD30 ligand in TH17 differentiation (2010)
  • Author(s): Sun X., et al.
  • Journal Title: J.Immunol Volume: 185 Pages: 2222-30
  • Peer Reviewed
• [Journal Article] CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses. (2010)
  • Author(s): Sun X., et al.
  • Journal Title: J.Immunol. Volume: 185 Pages: 7671-80
  • Peer Reviewed
• [Journal Article] Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation (2010)
  • Author(s): Gotoh K., et al.
  • Journal Title: J.Exp.Med. Volume: 207 Pages: 721-30
  • Peer Reviewed
• [Journal Article] Interleukin-15 is critical in the pathogenesis of influenza A virus-induced acute lung injury (2010)
  • Author(s): Nakamura R., et al.
  • Journal Title: J.Virol. Volume: 84 Pages: 5574-5582
  • Peer Reviewed
• [Journal Article] Exogenous IL-15 protects CD8+ T Cell Contraction after BCG vaccination but fails to provide protection against subsequent infection with Mycobacterium tuberculosis (2009)
  • Author(s): Tang C., Yamada H., Shibata K., Yoshida S., Wajjwalku W., and Yoshikai Y.
  • Journal Title: J. Leuko Biol Volume: 86 Pages: 187-94
• [Journal Article] Donor CD4 T cells are critical in allogeneic stem cell transplantation against murine solid tumor (2009)
  • Author(s): Kamiryo Y., , Eta M., Yamada H., Harano M., Yajima T., Harano M., Tatsugami K., Hamaguchi M., Takeuchi A., Naito S., and Yoshikai Y.
  • Journal Title: Cancer Research Volume: 69 Pages: 5151-8
• [Journal Article] L-Is is critical to the maintenance and functions of selfspecific memoryphenotype CD8 T cells (2009)
  • Author(s): Itsumi M., Yoshikai Y. and Yamada H
  • Journal Title: Eur J. Immunol Volume: 39 Pages: 1784-93
• [Journal Article] Oral administration of heatkilled Lactobacillus plantarum L-lsi enhances protection against influenza virus infection by stimulation of type I interferon production in mice (2009)
  • Author(s): Maeda M., Nakamura R., Hirose Y., Murosaki S., Yamamoto Y., Kase T. and Yoshikai Y
  • Journal Title: Int. Immunopharma Volume: 9 Pages: 1122-5
• [Journal Article] Protective role of Fas-FasL signaling in lethal infection with herpes simplex virus type 2 in mice (2009)
  • Author(s): Ishikawa T., Yamada H., Maeda Y., Goshima F., Nishiyama, Y. and Yoshikai Y.
  • Journal Title: J. viral Volume: 83 Pages: 11777-83
• [Journal Article] Oral administration of xanthan gum enhances antitumor activity through Toll-like receptor 4 (2009)
  • Author(s): Takeuchi A., Kamiryou Y., Yamada H., Eta M., Shibata K., Haruna K., Naito S., and Yoshikai Y.
  • Journal Title: Int. Immunopharma. Volume: 9 Pages: 1562-7
• [Journal Article] Tyrosine kinase 2 plays critical roles in the pathogenic CD4 T cell responses for the development of experimental autoimmune encephalomyelitis (2009)
  • Author(s): Oyamada A., Ikebe H., Itsumi M., Saiwai H., Okada, S., Shimoda, K., Iwakura, Y., Nakayama, K., Iwamoto, Y., Yoshikai, Y. and Yamada H.
  • Journal Title: J. Immuol Volume: 183 Pages: 7539-46
• [Journal Article] Direct recognition of mycobacterial cord factor, trehalose dimycolate, by C-type lect in Mincle (2009)
  • Author(s): Ishikawa E., Ishikawa T., Marita Y., Toyonaga K., Yamada H., Takeuchi 0., Akira S., Kinoshita T., Yoshikai Y. and Yamasaki S.
  • Journal Title: J. Exp. Med Volume: 206 Pages: 2879-88
• [Journal Article] Functions of ILliproducing y8 T cells The Open (2009)
  • Author(s): Shibata K. Yoshikai Y.
  • Journal Title: Immunology Journal Volume: 2 Pages: 151-155
• [Journal Article] Direct recognition of mycobacterial cord factor, trehalose dimy colate, by C-type lectin Mincle (2009)
  • Author(s): Ishikawa E., et al.
  • Journal Title: J. Exp. Med. 206 Pages: 2879-88
  • Peer Reviewed
• [Journal Article] Tyrosine kinase 2 plays critical roles in the pathogenic CD4T cell responses for the development of experimental autoimmune encephalomyelitis (2009)
  • Author(s): Oyamada A., et al.
  • Journal Title: J. Immunol. 183 Pages: 7539-46
  • Peer Reviewed
• [Journal Article] IL-15 is critical to the maintenance and functions of self-specific memory-phenotype CD8 T cells. (2009)
  • Author(s): Itsumi M., et al.
  • Journal Title: Eur J. Immunol. 39 Pages: 1784-93
  • Peer Reviewed
• [Journal Article] Exogenous IL-15 protects CD8+ T Cell Contraction after BCG vaccination but fails to provide protection against subsequent infection with Myco bacterium tuberculosis. (2009)
  • Author(s): Tang C., et al.
  • Journal Title: J. Leuko Biol. 86 Pages: 187-94
  • Peer Reviewed
• [Journal Article] Donor CD4 T cells are critical in allogeneic stem cell transplantation against murine solid tumor (2009)
  • Author(s): Kamiryo Y., et al.
  • Journal Title: Cancer Research 69 Pages: 5151-8
  • Peer Reviewed
• [Journal Article] FasL/Fas signal plays protective roles in lethal infection with herpes simplex virus type (2009)
  • Author(s): Ishikawa T., et al.
  • Journal Title: J. Virol. 83 Pages: 11777-83
  • Peer Reviewed
• [Journal Article] 炎症と免疫 (2009)
  • Author(s): 柴田健輔., 山田久方, 吉開泰信.
  • Journal Title: IL-17とγδ型Tリンパ球
• [Presentation] Notchr-Hes1経路は自然発生IL-17産生γδT細胞分化に必要である (2011)
  • Author(s): 柴田健輔、山田久方、吉開泰信
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇市
• [Presentation] 自然発生IL 17産生γδT細胞機能制御機構の解析 (2011)
  • Author(s): 中村真隆、柴田健輔、山田久方、吉開泰信
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇市
• [Presentation] 自然発生IL 17産生γδT細胞活性化におけるCDBOLigandの役割 (2011)
  • Author(s): 孫遜、郭穎、黄銀霞、柴田健輔、山田久方、吉開泰信
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇市
• [Presentation] Candi da al bi cans感染防御におけるIL-17産生γδT細胞の役割 (2011)
  • Author(s): 出嶋卓、柴田健輔、山田久方、吉開泰信
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇市
• [Presentation] Naturally occurri ng IL-17-producingγδT cells commit at the DN2 stage of mouse fetal thymus in Notch dependent nanner (2011)
  • Author(s): Shibata kensuke, Yanada Hsakata, Yoshi kai Yasunobu
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉市
• [Presentation] IL-7-receptor a rediated signaling is required for the devel opnent of naturally occurri ng IL-17-producingγδT cells in the adult thymus (2011)
  • Author(s): Nakamura Masataka, Shibata Kensuke, Yanada Hsakata, Ikuta Koichi, Yoshikai Yasunobu
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉市
• [Presentation] CD30L play an important role in early activation of naturally occurring γδ T cells producing IL-17 following bacterial infection (2011)
  • Author(s): Xun Sun, et al
  • Organizer: IUMS(国際細菌学会総会)
  • Place of Presentation: 札幌
• [Presentation] The Basic Helix-Loop-Helixprotein HES1, is required for the differentiation of naturally occurring (2010)
  • Author(s): Kensuke Shibata, Hsakata Yanada, Tetsuya Sato, Hromitsu Hara, Sho Yanasaki, Ryoichiro Kageyana, Yoichiro Iwakura, Hroyuki Toh and Yasunobu Yoshi kai
  • Organizer: interleukin(IL)-17-producing gd T cells. gd Tcell conference, Kiel
  • Place of Presentation: G rnanv
  • Year and Date: 2010-05-19
• [Presentation] CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice (2010)
  • Author(s): 孫遜
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸
• [Presentation] IL-15は自己抗原特異的CD8T細胞の維持や機能を制御する (2009)
  • Author(s): 逸見百江,吉開泰信,山田久方
  • Organizer: 第20回日本生体防御学会学術総会
  • Place of Presentation: 東京都
• [Presentation] BCG膀胱内注入療法の抗腫瘍効果にはγδT細胞によるIL 17産生が重要である (2009)
  • Author(s): 武内在雄,山田久方,柴田健輔,吉開泰信
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
• [Presentation] A novel role of CD30L/CD30 signaling by T-T cell interaction in Th1 response against mycobacterial infection (2009)
  • Author(s): Yoshikai Yasunobu
  • Organizer: US-JAPAN COOPERATIVE MEDICAL SCIENCE PROGRAM Forty-fourTuberculosis and Leprosy Research Conference,
  • Place of Presentation: Fukuoka
• [Book] 感染防御におけるIL 15, IL 17の役割(医学のあゆみ) (2011)
  • Author(s): 吉開泰信
• [Book] 免疫・アレルギーの理解のためのT細胞学(日本耳鼻科学会誌) (2011)
  • Author(s): 吉開泰信
• [Book] による記憶免疫活性化一アジュバントしてのIL 15への期待一アジュバント開発の新展開研究 (2011)
  • Author(s): 吉開泰信
  • Publisher: シーエムシー出版
• [Book] 戸田新細菌学改訂第34版 (2011)
  • Author(s): 吉開泰信
  • Publisher: 南山堂
• [Book] シンプル免疫学改訂第4版 (2011)
  • Author(s): 吉開泰信
  • Publisher: 南江堂
• [Book] IL-15,モデル動物利用マニュアル(疾患モデルの作成と利用:免疫疾患) (2011)
  • Author(s): 吉開泰信
  • Publisher: エル・アイ・シー
• [Book] 感染防御におけるIL-15,IL-17の役割 (2010)
  • Author(s): 吉開泰信
  • Publisher: 医学のあゆみvol234 No.5