Aanalysis of immune activation and protective mechanisms against infection using agonistic anti-TLR4 mAb

• Project/Area Number: 21590538
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Saga University
• Principal Investigator: KIMOTO Masao 佐賀大学, 医学部, 教授 (40153225)
• Co-Investigator(Kenkyū-buntansha): FUKUDOME Kenji 佐賀大学, 医学部, 准教授 (50284625) ; TSUKAMOTO Hiroki 佐賀大学, 医学部, 助教 (70423605)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 抗体 / 免疫賦活 / TLR4/MD-2 / LPS / 刺激型抗体 / 自然免疫 / 感染防御

Research Abstract

We analyzed the effects of agonistic anti-TLR4 mAb in vivo and in vitro. Anti-TLR4 agonistic mAb showed ajuvant effects in vivo. However, pre-injection of this agonistic mAb inhibited antibody production upon subsequent immunization. Cellular analysis revealed that this inhibitory effects was not due to the defect in antigen presentation to T cells but due to the defect in B cell priming. This finding will provide important information for the vaccine development and clinical use.

Research Products

• [Journal Article] The RP105/ MD-1 complex is indispensable for TLR4/ MD-2-dependent proliferation and IgM-secreting plasma cell differentiation of marginal zone B cells (2012)
  • Author(s): Nagai Y, Yanagibashi T, Watanabe Y, Ikutani M, Kariyone A, Ohta S, Hirai Y, Kimoto M, Miyake K, Takatsu K.
  • Journal Title: Int Immunol Volume: (in press)
• [Journal Article] Multiple potential regulatory sites of TLR4 activation induced by LPS as revealed by novel inhibitory human TLR4 mAbs (2012)
  • Author(s): Tsukamoto H, Fukudome K, Takao S, .
  • Journal Title: Int Immunol Volume: (in press)
• [Journal Article] Arai H, Kadowaki T, Nagai R.: Saturated Fatty Acid and TLR Signaling LinkβCell Dysfunction and Islet Inflammation (2012)
  • Author(s): Eguchi K, Manabe I, Oishi-Tanaka Y, Ohsugi M, Kono N, Ogata F, Yagi N, Ohto U, Kimoto M, Miyake K, Tobe K, Arai H, Kadowaki T, Nagai R.
  • Journal Title: Cell Metab Volume: (in press)
• [Journal Article] Multiple potential regulatory sites of TLR4 activation induced by LPS as revealed by novel inhibitory human TLR4 mAbs (2012)
  • Author(s): Tsukamoto H
  • Journal Title: Int Immunol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Saturated Fatty Acid and TLR Signaling Link ss Cell Dysfunction and Islet Inflammation (2012)
  • Author(s): Eguchi K
  • Journal Title: Cell Metab Volume: (in press)
  • Peer Reviewed
• [Journal Article] The RP105/MD-1 complex is indispensable for TLR4/MD-2-dependent proliferation and IgM-secreting plasma cell differentiation of marginal zone B cells (2012)
  • Author(s): Nagai Y
  • Journal Title: Int Immunol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells (2010)
  • Author(s): Tsukamoto H, Fukudome K, Takao S, Tsuneyoshi N, Kimoto M.
  • Journal Title: Int Immunol Volume: 22(4) Pages: 271-80
  • NAID: 10027392279
• [Journal Article] Organotypic culture of human bone marrow adipose tissue (2010)
  • Author(s): Uchihashi K, Aoki S, Shigematsu M, Kamochi N, Sonoda E, Soejima H, Fukudome K, Sugihara H, Hotokebuchi T, Toda S
  • Journal Title: Pathol Int Volume: 60(4) Pages: 259-67
  • NAID: 10029331372
• [Journal Article] Blocking endothelial protein C receptor(EPCR) accelerates thrombus development in vivo (2010)
  • Author(s): Centelles MN, Puy C, Lopez-Sagaseta J, Fukudome K, Montes R, Hermida J.
  • Journal Title: Thromb Haemost Volume: 103(6) Pages: 1239-44
• [Journal Article] Activated protein C utilizes the angiopoietin/ Tie2 axis to promote endothelial barrier function (2010)
  • Author(s): Minhas N, Xue M, Fukudome K, Jackson CJ.
  • Journal Title: FASEB J Volume: 24(3) Pages: 873-81
• [Journal Article] Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells (2010)
  • Author(s): Matsushita H, Ohta S, Shiraishi H, Suzuki S, Arima K, Toda S, Tanaka H, Nagai H, Kimoto M, Inokuchi A, Izuhara K.
  • Journal Title: Int Immunol Volume: 22(9) Pages: 739-47
  • NAID: 10030913704
• [Journal Article] Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells. (2010)
  • Author(s): Tsukamoto H
  • Journal Title: Int Immunol. Volume: 22(4) Pages: 271-280
  • NAID: 10027392279
  • Peer Reviewed
• [Journal Article] Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells. (2010)
  • Author(s): Matsushita H
  • Journal Title: Int Immunol. Volume: 22(9) Pages: 739-747
  • Peer Reviewed
• [Journal Article] Organotypic culture of human bone marrow adipose tissue. (2010)
  • Author(s): Uchihashi K
  • Journal Title: Pathol Int. Volume: 60(4) Pages: 259-267
  • Peer Reviewed
• [Journal Article] Lopez-Sagaseta J, Fukudome K, Montes R, Hermida J.: Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo. (2010)
  • Author(s): Centelles MN
  • Journal Title: Thromb Haemost. Volume: 103(6) Pages: 1239-1244
  • Peer Reviewed
• [Journal Article] Activated protein C utilizes the angiopoietin/Tie2 axis to promote endothelial barrier function. (2010)
  • Author(s): Minhas N
  • Journal Title: FASEB J. Volume: 24(3) Pages: 873-881
  • Peer Reviewed
• [Journal Article] Effect of disease activity and corticosteroids on protein C receptor in patients with systemic lupus erythematosus (2009)
  • Author(s): Koarada S, Tsuneyoshi N, Haruta Y, Tada Y, Mitamura M, Inoue H, Ohta A, Fukudome K, Nagasawa K.
  • Journal Title: Mod Rheumatol Volume: 19(2) Pages: 173-9
• [Journal Article] Effect of disease activity and corticosteroids on serum levels of soluble endothelial cell protein C receptor in patients with systemic lupus erythematosus. 2009 (2009)
  • Author(s): Koarada S
  • Journal Title: Mod Rheumatol. Volume: 19(2) Pages: 173-179
  • Peer Reviewed
• [Presentation] Inhibition of primary but not secondary humoral immune responses by pre-injection of an agonistic anti-TLR4/ MD-2 antibody (2011)
  • Author(s): Rachmawati NM, Fukudome K, Tsuneyoshi N, Uleng B, Ohta S, Kimoto M
  • Organizer: 第40回日本免疫学会
  • Year and Date: 2011-11-28
• [Presentation] Inhibition of primary but not secondary humoral immune responses by pre-injection of an agonistic anti-TLR4/MD-2 antibody (2011)
  • Author(s): Rachmawati NM
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-28
• [Presentation] Agonistic anti-TLR4 monoclonal antibodies function as immunoadjuvants (2010)
  • Author(s): Rachmawati NM, Uleng B, Fukudome K, Kimoto M
  • Organizer: 第14回国際免疫学会議
  • Year and Date: 2010-08-27
• [Presentation] Lipopolysaccharide-bindingprotein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells (2010)
  • Author(s): Tsukamoto H, Fukudome K, Takao S, Tsuneyoshi N, Kimoto M.
  • Organizer: 第14回国際免疫学会議
  • Year and Date: 2010-08-27
• [Presentation] Agonistic anti-TLR4 monoclonal antibodies function as immunoadjuvants. (2010)
  • Author(s): Rachmawati NM
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Presentation] Lipopolysaccharide-bindingprotein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells. (2010)
  • Author(s): Tsukamoto H
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Book] 医学大辞典.第2版
  • Author(s): 木本雅夫.伊藤正男, 井村裕夫, 高久史麿
  • Publisher: 医学書院
• [Remarks] ホームページ
  • URL: http://www.biomol.med.saga-u.ac.jp/immunol/index.htm