A classification and identification of the asthmatic disease-inducedCD4 T cell subset with costimulatory molecule marker

• Project/Area Number: 22591098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Juntendo University
• Principal Investigator: AKIBA Hisaya 順天堂大学, 医学研究科, 准教授 (60338316)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 補助シグナル分子 / Th1/Th2 / 喘息モデルマウス / 関節炎モデルマウス / TIM-4 / 関節炎マウス / CD70-CD27 / T細胞分化 / コラーゲン誘発性関節炎マウス

Research Abstract

We revealed that antigen-specific CD4 T cells were separated into CD27+and CD27-populations in the lymph node from OVA-immunized DO11.10/Rag-2-/-mice.The CD27+CD4 T cells produced a high level of IFN-・, representing Th1 cells. In contrast, CD27-CD4 T cells produced high levels of IL-4, IL-5, and IL-13, representing Th2 cells.Eosinophil infiltration and Th2 cytokine production in the lung and the population of CD27-Th2 cells was significantly reduced by the anti-CD70 mAb treatment. These results indicated an important role for CD27 in the development of pathogenic Th2 cells in a murine model of allergic lung inflammation.

Research Products

• [Journal Article] Blockade of CD70-CD27 Interaction Inhibits Induction of Allergic Lung Inflammation in Mice (2012)
  • Author(s): Makino F, Ito J, Abe Y, Harada N, Kamachi F, Yagita H, Takahashi K, Okumura K, Akiba H
  • Journal Title: American journal of respiratory cell and molecular biology Volume: 47 Issue: 3 Pages: 298-305
  • DOI: 10.1165/rcmb.2011-0354oc
  • Peer Reviewed
• [Journal Article] Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. S. (2012)
  • Author(s): Chiba, M. Baghdadi, H. Akiba, H. Yoshiyama, I. Kinoshita, H. Dosaka-Akita, Y. Fujioka, Y. Ohba, J. V. Gorman, J. D. Colgan, M. Hirashima, T. Uede, A. Takaoka, H. Yagita and M. Jinushi.
  • Journal Title: Nat. Immunol. Volume: 13 Issue: 9 Pages: 832-842
  • DOI: 10.1038/ni.2376
  • Peer Reviewed
• [Journal Article] Galectin-9 and T cell immunoglobulin mucin-3 pathway is a therapeutic target for type 1 diabetes. (2012)
  • Author(s): Kanzaki M
  • Journal Title: Endocrinology Volume: 153(2) Issue: 2 Pages: 612-620
  • DOI: 10.1210/en.2011-1579
  • Peer Reviewed
• [Journal Article] Expression pattern changes and function of RANKL during mouse lymph node microarchitecture development (2012)
  • Author(s): Sugiyama, et al.
  • Journal Title: International Immunology Volume: 24 Issue: 6 Pages: 369-378
  • DOI: 10.1093/intimm/dxs002
  • Peer Reviewed
• [Journal Article] Antibodies against B7-DC with differential binding properties exert opposite effects (2012)
  • Author(s): Ritprajak P, Hashiguchi M, Akiba H, Yagita H, Okumura K, Azuma M
  • Journal Title: Hybridoma Volume: 31 Issue: 1 Pages: 40-47
  • DOI: 10.1089/hyb.2011.0087
  • Peer Reviewed
• [Journal Article] EndogenousTim-1 promotes T-cell responses and cell-mediated injury in experimental crescentic glomerulonephritis (2012)
  • Author(s): ozaki Y, Nikolic-Paterson DJ, Snelgrove SL, Akiba H, Yagita H,Holdsworth SR, Kitching AR
  • Journal Title: Kidney international Volume: 81 Issue: 9 Pages: 844-855
  • DOI: 10.1038/ki.2011.424
  • Peer Reviewed
• [Journal Article] TIM-1 signaling in B cells regulates antibody production (2012)
  • Author(s): Ma J, Usui Y, Takeda K, Harada N, Yagita H, Okumura K, Akiba H
  • Journal Title: iochem Biophys Res Commun Volume: 406 Issue: 2 Pages: 223-228
  • DOI: 10.1016/j.bbrc.2011.02.021
  • Peer Reviewed
• [Journal Article] Anti-TIM-2 monoclonal antibody exacerbates collagen-induced arthritis by stimulating B cells (2011)
  • Author(s): Kawamoto T, Abe Y, Ito J, Makino F, Kojima Y, Usui Y, Ma J, Morimoto S, Yagita H, Okumura K, Takasaki Y, Akiba H
  • Journal Title: Arthritis Res Ther Volume: 13 Issue: 2
  • DOI: 10.1186/ar3288
  • Peer Reviewed
• [Journal Article] The TIM-1:TIM-4 pathway enhances renal ischemia-reperfusion injury (2011)
  • Author(s): Rong S, Park JK, Kirsch T, Yagita H, Akiba H, Boenisch O, Haller H, Najafian N, Habicht A
  • Journal Title: J Am Soc Nephrol Volume: 22 Issue: 3 Pages: 484-495
  • DOI: 10.1681/asn.2010030321
  • Peer Reviewed
• [Journal Article] Tim-1 promotes cisplatin nephrotoxicity (2011)
  • Author(s): Nozaki Y, Nikolic-Paterson DJ, Yagita H, Akiba H, Holdsworth SR, Kitching AR
  • Journal Title: Am J Physiol Renal Physiol Volume: 301 Issue: 5 Pages: F1098-F1104
  • DOI: 10.1152/ajprenal.00193.2011
  • Peer Reviewed
• [Journal Article] Anti-TIM3 antibody promotes T cell IFN-γ-mediated anti-tumor immunity and suppresses established tumors (2011)
  • Author(s): Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ
  • Journal Title: Cancer Res Volume: 71 Issue: 10 Pages: 3540-3551
  • DOI: 10.1158/0008-5472.can-11-0096
  • Peer Reviewed
• [Journal Article] Wound-induced TGF-γ1 and TGF-γ2 enhance airway epithelial repair via HB-EGF and TGF-α. (2011)
  • Author(s): Ito J, Harada N, Nagashima O, Makino F, Usui Y, Yagita H, Okumura K, Dorscheid DR, Atsuta R, Akiba H, Takahashi K
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Issue: 1 Pages: 109-114
  • DOI: 10.1016/j.bbrc.2011.07.054
  • Peer Reviewed
• [Journal Article] Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice (2011)
  • Author(s): Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, Chalasani G, Sayegh MH, Najafian N, Rothstein DM
  • Journal Title: J Clin Invest Volume: 121 Issue: 9 Pages: 3645-3656
  • DOI: 10.1172/jci46274
  • Peer Reviewed
• [Journal Article] TIM1 is an endogenous ligand for LMIR5/CD300b: LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury (2010)
  • Author(s): Yamanishi Y, Kitaura J, Izawa K, Kaitani A, Komeno Y, Nakamura M, Yamazaki S, Enomoto Y, Oki T, Akiba H, Abe T, Komori T, Morikawa Y, Kiyonari H, Takai T, Okumura K, Kitamura T.
  • Journal Title: J Exp Med Volume: 207 Issue: 7 Pages: 1501-1511
  • DOI: 10.1084/jem.20090581
  • Peer Reviewed
• [Journal Article] Expression and function of inducible costimulator on peripheral blood CD4+T cells in Behcet's patients with uveitis: a new activity marker? (2010)
  • Author(s): Usui Y, Takeuchi M, Yamakawa N, Takeuchi A, Kezuka T, Ma J, Matsuda R, Okunuki Y, Akiba H, Goto H
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 51 Issue: 10 Pages: 5099-5104
  • DOI: 10.1167/iovs.10-5286
  • Peer Reviewed
• [Journal Article] TIM-3 determines severity of liver ischemia/reperfusion injury in mice in a TLR4-dependent manner (2010)
  • Author(s): Uchida Y, Ke B, Freitas MC, Yagita H,Akiba H, Busuttil RW, Najafian N, Kupiec-Weglinski JW
  • Journal Title: Gastroenterology Volume: 139 Issue: 6 Pages: 2195-2206
  • DOI: 10.1053/j.gastro.2010.07.003
  • Peer Reviewed
• [Journal Article] The emerging role of TIM-1 in the mechanism of liver ischemia and reperfusion injury in the mouse (2010)
  • Author(s): Uchida Y, Ke B, Freitas MC, Ji H, Zhao D, Benjamin ER, Najafian N, Yagita H, Akiba H, Busuttil RW, Kupiec-Weglinski JW
  • Journal Title: Hepatolog Volume: 51 Issue: 4 Pages: 1363-1372
  • DOI: 10.1002/hep.23442
  • Peer Reviewed
• [Journal Article] Premature terminal exhaustion of Friend virus-specific effector CD8^+T cells by rapid induction of multiple inhibitory receptors (2010)
  • Author(s): Takamura, S., S. Tsuji-Kawahara, H. Yagita, H. Akiba, M. Sakamoto, T. Chikaishi, M. Kato, M. Miyazawa
  • Journal Title: J. Immunol Volume: 184 Issue: 9 Pages: 4696-4707
  • DOI: 10.4049/jimmunol.0903478
  • Peer Reviewed
• [Journal Article] Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD (2010)
  • Author(s): Fujimura J, Takeda K, Kaduka Y, Saito M, Akiba H, Yagita H, Yamashiro Y, Shimizu T, Okumura K
  • Journal Title: Pediatr Transplant Volume: 14 Issue: 4 Pages: 540-548
  • DOI: 10.1111/j.1399-3046.2009.01279.x
  • Peer Reviewed
• [Journal Article] IM-3: a novel regulatory molecule of alloimmune activation (2010)
  • Author(s): Boenisch O, D'Addio F, Watanabe T, Elyaman W, Magee CN, Yeung MY, Padera RF, Rodig SJ, Murayama T, Tanaka K, Yuan X, Ueno T, Jurisch A, Mfarrej B, Akiba H, Yagita H, Najafian N
  • Journal Title: J Immunol Volume: 185 Issue: 10 Pages: 5806-5819
  • DOI: 10.4049/jimmunol.0903435
  • Peer Reviewed
• [Journal Article] Expression and function of inducible costimulator on peripheral blood CD4^+ T cells in Behcet's patients with uveitis : a new activity marker? (2010)
  • Author(s): Usui, Y
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 51 Pages: 5099-5104
  • Peer Reviewed
• [Journal Article] TIM-3 : a novel regulatory molecule of alloimmune activation. (2010)
  • Author(s): Boenisch, O
  • Journal Title: J Immunol Volume: 185 Pages: 5806-5819
  • Peer Reviewed
• [Journal Article] Premature terminal exhaustion of Friend virus-specific effector CD8^+ T cells by rapid induction of multiple inhibitory receptors. (2010)
  • Author(s): Takamura, S
  • Journal Title: J Immunol Volume: 184 Pages: 4696-4707
  • Peer Reviewed
• [Journal Article] Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD. (2010)
  • Author(s): Fujimura, J
  • Journal Title: Pediatr Transplant Volume: 14 Pages: 540-548
  • Peer Reviewed
• [Journal Article] TIM1 is an endogenous ligand for LMIR5/CD300b : LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury. (2010)
  • Author(s): Yamanishi, Y
  • Journal Title: J Exp Med Volume: 207 Pages: 1501-1511
  • Peer Reviewed
• [Journal Article] TIM-3 determines severity of liver ischemia/reperfusion injury in mice in a TLR4-dependent manner. (2010)
  • Author(s): Uchida, Y
  • Journal Title: Gastroenterology Volume: 139 Pages: 2195-2206
  • Peer Reviewed
• [Journal Article] The emerging role of TIM-1 in the mechanism of liver ischemia and reperfusion injury in the mouse. (2010)
  • Author(s): Uchida, Y
  • Journal Title: Hepatology Volume: 51 Pages: 1363-1372
  • Peer Reviewed
• [Presentation] Therapeutic effect of anti-TIM-4 mAb in mouse models of arthritis. (2012)
  • Author(s): Yoshiyuki Abe
  • Organizer: The 8th International Congress on Autoimmunity
  • Place of Presentation: Granada, Spain
• [Presentation] マウス関節炎におけるTIM-4の病態関与:増悪と抑制 (2012)
  • Author(s): 秋葉 久弥
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東 京・グランドプリンスホテル新高輪
  • Invited
• [Presentation] Anti-TIM-4 mAb ameliorates allergic lung inflammation by inhibiting TIM-4-mediated mast cell stimulation. (2012)
  • Author(s): KAMACHI Fumitaka
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] TIM-4 blockade augments therapeutic efficacy of chemotherapy by immune-mediated mechanisms. (2012)
  • Author(s): Muhammad Baghdadi
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Suppression of corneal graft rejection by blocking CD27/CD70. (2012)
  • Author(s): Motohashi R
  • Organizer: ARVO
  • Place of Presentation: Fort Lauderdale, Florida
• [Presentation] Expression and function of inducible costimulator on peripheral blood CD4 T cells in patients with ocular Behcets disease: a new activity marker? (2012)
  • Author(s): Yoshihiko Usui
  • Organizer: 15th International Conference on Behcet’s disease
  • Place of Presentation: Yokohama
• [Presentation] CD70-CD27 Interaction Regulates Asthmatic Response in a Murine Model of Asthma (2011)
  • Author(s): Fumihiko Makino
  • Organizer: XXII World Allergy Congress
  • Place of Presentation: Cancun Center (Mexico)
  • Year and Date: 2011-12-05
• [Presentation] Complicated Expression Profiles of RANKL and Its Function in Peripheral Lymphoid Organs Development (2011)
  • Author(s): SUGIYAMA Machiko
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-29
• [Presentation] TIM-4 has two different functions in mouse models of arthritis (2011)
  • Author(s): ABE Yoshiyuki
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-28
• [Presentation] Tumor-associated dendritic cells suppress nucleic acids-mediated innate immune recognition by TIM-3-dependent mechanisms (2011)
  • Author(s): JINUSHI Masahisa
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-27
• [Presentation] 抗CD70抗体投与によるOVA誘発性喘息マウスの発症抑制とそのメカニズムの解析 (2011)
  • Author(s): 牧野文彦
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: グランドプリンスホテル新高輪(東京)
  • Year and Date: 2011-11-10
• [Presentation] 抗CD70抗体投与によるOVA誘発性マウス喘息疾患の発症抑制とそのメカニズムの解明 (2011)
  • Author(s): 牧野文彦
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2011-04-24
• [Presentation] Secretion of wound-induced TGF-β1 and TGF-β2 enhance airway epithelial wound repair via HB-EGF and TGF-α. (2010)
  • Author(s): Ito, J.
  • Organizer: European Respiratory Society Annual Congress Barcelona 2010
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-09-19
• [Presentation] マウス脈絡膜新生血管モデルに対するCD40の関与 (2010)
  • Author(s): 横井克俊
  • Organizer: 第165回東京医科大学医学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-06-05
• [Presentation] TIM-4の喘息モデルマウスにおける役割の検討 (2010)
  • Author(s): 伊藤潤
  • Organizer: 第50回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会議場
  • Year and Date: 2010-04-24
• [Presentation] TIM4 regulates asthmatic response in a murine model of asthma. (2010)
  • Author(s): Ito, J.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] CD70-CD27 interaction regulates asthmatic response in a murine model of asthma. (2010)
  • Author(s): Makino, F.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] Anti-TIM-2 mAb exacerbates collagen-induced arthritis by stimulating B cells. (2010)
  • Author(s): Abe, Y.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] Secretion of wound-induced TGF-β1 and TGF-β2 enhance airway epithelial repair via HB-EGF and TGF-α. (2010)
  • Author(s): Harada, N.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] TIM1 is an endogenous ligand for IMIR5/CD300b : LMIR5 deficiency ameliorates kidney ischemia/reperfusion injury. (2010)
  • Author(s): Yamanishi, Y.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] Premature terminal exhaustion of Friend virus-specific effector CD8^+ T cells by rapid induction of multiple inhibitory receptors (2010)
  • Author(s): Takamura, S.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] Antibodies against B7-DC with differential binding properties exert opposite effects : Implication of dual functions in PD-1 and B7-DC interactions. (2010)
  • Author(s): Azuma, M.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] RANKL is a critical factor for the differentiation, maintenance, and survival of antigen-sampling M cells in the intestine. (2010)
  • Author(s): Knoop, K.A.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場
• [Presentation] Expression and Function of Inducible Costimulator in Patients with Ocular Behcet's Disease : Possible Involvement in IFN and IL-17 Production. (2010)
  • Author(s): Usui, Y.
  • Organizer: Annual meeting of the ARVO(Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale, USA
• [Presentation] The Role of CD40/CD40L Costimulatory pathway in experimental induced choroidal neovascularization. (2010)
  • Author(s): Umazume, K.
  • Organizer: Annual meeting of the ARVO(Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Fort Lauderdale, USA
• [Presentation] マウス脈絡膜新生血管モデルに対するCD40の関与 (2010)
  • Author(s): 馬詰和比古
  • Organizer: 第114回日本眼科学会総会
  • Place of Presentation: 名古屋国際会議場
• [Remarks] ホームページ情報
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/meneki/home.html
• [Remarks] 順天堂大学医学部免疫学
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/meneki/home.html