• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Studies on regulatory mechanism of Th1/Th2 cell differentiation by antigen presenting cell (APC) and onAPC-mediated immunotherapy

Research Project

Project/Area Number 16208031
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical veterinary science
Research InstitutionThe University of Tokyo

Principal Investigator

ONO Kenichiro  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor (50111480)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Yoshitsugu  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor (00173922)
MATSUKI Naoaki  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor (40251417)
SHIMADA Terumasa  Obihiro University, Department of Veterinary Science, Professor (00264812)
WASHIZU Tsukimi  Nippon Vetarinaiy and Life Science University, Department of Veterinary Science, Professor (20191736)
BONKOBARA Mkoto  Nippon Vetarinaiy and Life Science University, Department of Veterinary Science, Lecturer (50343611)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥49,790,000 (Direct Cost: ¥38,300,000、Indirect Cost: ¥11,490,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2006: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2005: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2004: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
KeywordsAntigen presenting cell / Dendritic cell / Established cell / Stimulating factor / Th1 / Th2 cell differentiation / Induction into Th1 / Th2 cell / Malignant melanoma / Babesiosis / Dndritic cell-mediated therapy / 分化・誘導 / Th2分化・誘導 / Th2 / 細胞免疫療法
Research Abstract

Regulatory mechanisms of Th1/Th2 cell differentiation by antigen presenting cell (APC) and APC-mediated immunotherapy were investigated for 3 years (from 2004 to 2007) and following results were obtained.
1) Th1/Th2 cell differentiation in certain diseases, such as murine babesiosis, and canine malignant melanoma and histiocytic sarcoma:
a) IL-12p70 production from APC (included splenic macrophages) induced Th1 cell differentiation and closely related to transient parasitemia in Babesia microti infection. IL-12p70 was suggested to be an important factor for eliminating Babesia microti.
b) Seven novel cell lines from canine histiocytic sarcoma were established. All of them showed phagocytic and processing activities, suggesting to be a mononuclear phagocytic system cell and also APC.
2) Stimulatory factors for Th1/Th2 cell differentiation:
a) Stimulatory factors for IL-12 production, by which Th1 cell differentiation was introduced, from macrophages were isolated and purified from culture medium of Babesia microti and Babesia rodhaini infected erythrocytes. These factors were heat stable and soluble and their elution profiles were quite different between Babesia microti and Babesia rodhaini cultured medium.
3) APC-mediated immunotherapy
a) Against canine malignant melanoma: Canine APC from bone marrow were pulsed with lysate o canine melanoma cell lines and were transplanted into clinically healthy dogs. APC induced cell-mediated immunological responses against melanoma cells and prolonged survival period.
b) Against Babesia microti and Babesia rodhaini. Murine bone marrow-derived APC pulsed with Babesia microti infected erythrocytes induced decrease of parasitemia and increased survival rate in mice infected with Babesia rodhaini. These results suggested that APC-mediated therapy is an available manner for protozoan and cancer diseases.

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (51 results)

All 2008 2007 2006 2005 2004

All Journal Article (51 results) (of which Peer Reviewed: 21 results)

  • [Journal Article] Induction of dendric cell-mediated immune response against canine malignant melanoma cells.2008

    • Author(s)
      Tamura, K. et al.
    • Journal Title

      Vet. J. 175

      Pages: 126-129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of canine Kdap in normal, hyperplastic and neoplastic epidermis.2008

    • Author(s)
      Yagihara, H. et al.
    • Journal Title

      Vet. J. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Strain differences on splenic IL-12p70 concentration ahd immunological responsesin mice infected with Babesia microti and Babesia rodhaini2008

    • Author(s)
      Ohmori, T. et al.
    • Journal Title

      J. Protozool. Res. (準備中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Immunological responses in anti-IL-12p70 serum treated and in IL-12 knock out mice infected muth Babesia microti and Babesia rodhaini.2008

    • Author(s)
      Ohmori, T. et al.
    • Journal Title

      J. Protozool. Res. (準備中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Comparison of surface markers among among 7 cell lines from canine histiocytic sarcoms.2008

    • Author(s)
      Azagami, D. et al.
    • Journal Title

      J. Vet. Med. Sci. l. (準備中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Induction of dendritic cell-mediated immune response against Babesia microti and Babesia rodhaini.2008

    • Author(s)
      Tokushuge, H. et al.
    • Journal Title

      J. Protozool. Res. (準備中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Changes surface markers on 7 canine histiocytic sarcoma cell lines by cultivation with GM-CSF and IL-4.2008

    • Author(s)
      Azagami, D. et al.
    • Journal Title

      J. Vet. Med. Sci. (準備中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of pulsed dendritic cell treatment on paraistemia and survival rate in mice infected with Babesia microti and Babesia rodhaini2008

    • Author(s)
      Tokushuge, H. et al.
    • Journal Title

      J. Protozool. Res. (準備中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Induction of dendric cell-mediated immune response against canine malignant melanoma cells2008

    • Author(s)
      Tamura, K., Yamada, M., Isotani, M., Arai, H., Yagihara, H., Ono, K., Washizu, T., Bonkobara, M.
    • Journal Title

      Vet. J. 175

      Pages: 126-129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of canine Kdap in normal, hyperplastic and neoplastic epidermis2008

    • Author(s)
      Yagihara, H., Kinjo, E., Kobayashi, Y., Tsuji, A., Nishimura, Y., Shinozaki, N., Tamura, K., Isotani, M., Nakagaki, K., Takahashi, K, Ono, K, Washizu, T., Bonkobara, M.
    • Journal Title

      Vet. J. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Strain differences on splenic IL-12p70 concentration and immunological responses in mice infected with Babesia microti and Babesia rodhaini2008

    • Author(s)
      Ohmori, T., Tamahara, S., Pham, N. T., Tomihari, M., Matsuki, N., Ono, K.
    • Journal Title

      J. Protozool. Res. (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Immunological responses in anti-IL-12p70 serum treated and in IL-12p70 knockout mice infected with Babesia microti and Babesia rodhaini2008

    • Author(s)
      Ohmori, T., Tamahara, S., Tomihari, M., Matsuki, N., Ono, K.
    • Journal Title

      J. Protozool. Res. (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Comparison of surface markers among 7 cell lines from canine histiocytic sarcoma2008

    • Author(s)
      Azakami, D., Bonkobara, Washizu, T., Matsuki, N., Ono, K.
    • Journal Title

      J. Vet. Med. Sci. (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Induction of dendric cell-mediated immune response against Babesia microti and Babesia rodhaini2008

    • Author(s)
      Tokushige, H., Ohmori, T., Tamahara, S., Tomihari, M., Matsuki, N., Ono, K.
    • Journal Title

      J. Protozool. Res. (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Changes of surface markers on 7 canine histiocytic sarcoma cell lines by cultivation with GM-CSF and IL-42008

    • Author(s)
      Azakami, D., Bonkobara, Washizu, T., Matsuki, N., Ono, K.
    • Journal Title

      J. Vet. Med. Sci. (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of pulsed dendric cell treatment on parasitemia and survival rate in mice infected with Babesia microti and Babesia rodhaini2008

    • Author(s)
      Tokushige, H., Ohmori, T., Tamahara, S., Tomihari, M., Matsuki, N., Ono, K.
    • Journal Title

      J. Protozool. Res. (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Induction of dendric cell-mediated immune response a gainst canine malignant melanoma cells2008

    • Author(s)
      Tamura, K, et. al.
    • Journal Title

      Vet.J 175

      Pages: 126-129

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of dendric cell-mediated immune responses among canine malignant cells2008

    • Author(s)
      Tamura, K, et. al.
    • Journal Title

      J.Vet.Med.Sci

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression pattern of the BRCA1 splicing variants in canine normal tis sues and mammary tumor.2007

    • Author(s)
      Sugiura, T. et al.
    • Journal Title

      J. Vet. Med. Sci. 69

      Pages: 587-592

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Comparison of dendric cell-mediated immune responses among canine malignant cells2007

    • Author(s)
      Tamura, K. et al.
    • Journal Title

      J. Vet. Med. Sci. 69

      Pages: 925-930

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression pattern of the BRCA1 splicing variants in canine normal tissues and mammary gland tumor2007

    • Author(s)
      Sugiura, T., Matsuyama, S., Akiyoshi, H., Yamate, J., Kuwamura, M., Aoki, M., Shimada, T., Ohashi, F., Kubo, K.
    • Journal Title

      J. Vet. Med Sci. 69

      Pages: 587-592

    • NAID

      110006318093

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Comparison of dendric cell-mediated immune responses among canine malignant cells2007

    • Author(s)
      Tamura, K., Arai, H., Ueno, E., Saito, C., Yagihara, H., Isotani, M., Ono., K, Washizu, T., Bonkobara, M.
    • Journal Title

      J. Vet. Med. Sci. 69

      Pages: 925-930

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Genomic organization of the T-cell receptor γ gene and PCR detection of its clonal rearrangement in canine T-cell lymhoma/leukemmia2007

    • Author(s)
      Yagihara, H, et. al.
    • Journal Title

      Vet.Immunol.Immunopathol 115

      Pages: 375-382

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and cornification-related gene expression of canine keratinocyte differentiation-associated protein, Kdap.2006

    • Author(s)
      Yagihara, H. et al.
    • Journal Title

      Vet. J. 172

      Pages: 141-146

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Efficient generation of canine bone marrow-derived dendric cells2006

    • Author(s)
      Isotani, M. et al.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 809-814

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Establishment and biological characterization of canine histiocytic sarcoma cell lines.2006

    • Author(s)
      Azagami, D. et al.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 1343-1346

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and cornification-related gene expression of canine keratinocyte differentiation-associated protein, Kdap2006

    • Author(s)
      Yagihara, H., Terada, Y., Sugimoto, S., Hidaka, F., Yamada, O., Ono, K., Washizu, T., Ariizumi, K., Bonkobara, M.
    • Journal Title

      Vet. J. 172

      Pages: 141-146

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Efficient generation of canine bone marrow-derived dendric cells2006

    • Author(s)
      Isotani, M., Katsuma, K, Tamura, K., Yamada, M., Yagihara, H., Azagami, D., Ono, K., Washizu, T., Bonkobara, M.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 809-814

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Establishment and biological characterization of canine histiocytic sarcoma cell lines2006

    • Author(s)
      Azakami, D., Bonkobara, M., Iida, A., Hiraiwa, M., Kato, R., Niikura, Y., Iwaki, S., Washizu, T., Matsuki, N., Ono, K.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 1343-1346

    • NAID

      130000447983

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Establishment and biological characterization of canine histiocytic sarcoma cell lines2006

    • Author(s)
      Azagami.D, et. al.
    • Journal Title

      J.Vet.Med.Sci 68

      Pages: 1343-1346

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of the polymerase chain reaction assay based on the canine genome database forr detection of monoclonality in B cell lymphoma.2006

    • Author(s)
      Tamura, K. et al.
    • Journal Title

      Vet. Immunol. Immunopathol. 110

      Pages: 163-167

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of parathyroid hormone related peptide (PTHrP) mRNA in mammary gland in cows.2006

    • Author(s)
      Onda, K. et al.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 9-13

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification and comification-related gene expression of canine keratinocyte differentiation-associated protein, Kdap.2006

    • Author(s)
      Yagihara, H. et al.
    • Journal Title

      Vet. J. 172

      Pages: 141-146

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Efficient generation of canine bone marrow-derived dendric cells.2006

    • Author(s)
      Isotani, M. et al.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 809-814

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Isentification of ac・kit exon 8 internal tandem duplication in a feline mast cell tumor case and its favorable response to the tyrosine kinase inhibitor imatinib mesylate.2006

    • Author(s)
      Isotani, M. et al.
    • Journal Title

      Vet. Immunol. Immunopathol, 114

      Pages: 168-172

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Development of the polymerase chain reaction assay based on the canine genome database for detection of monoclonality in B cell lymphoma.2006

    • Author(s)
      Tamura, K. et al.
    • Journal Title

      Vet.Immunol.Immunopathol. 110

      Pages: 163-167

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Stimulatory factors for Interleukin-12 Production from Murine Splenic Macrophages Co-cultured with Babesia rodhaini and Babesia microti Infected Erythrocytes.2006

    • Author(s)
      Hashiguchi-Kato, R. et al.
    • Journal Title

      J.Protozool.Res. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Changes of splenic interleukin-12p70 1evels in mice infected with Babesia microti and Babesia rodhaini.2005

    • Author(s)
      Ohmori, T. et al.
    • Journal Title

      J. Protozool. Res. 15

      Pages: 41-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Stimulatory, factors for InterIeukin-12 Production from murine splenic macrophages co-cultured with Babesia rodhaini and Babesia microti infected erythrocytes.2005

    • Author(s)
      Hashiguchi-Kato, R. et al.
    • Journal Title

      J. Protozool. Res. 15

      Pages: 48-56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Changes of splenic interleukin-12p70 levels in mice infected with Babesia microti and Babesia rodhaini2005

    • Author(s)
      Ohmori, T., Tamahara, S., Pham, N. T., Tomihari, M., Matsuki, N., Ono, K.
    • Journal Title

      J. Protozool. Res. 15

      Pages: 41-47

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Stimulatory factors for Interleukin-12 Production from murine splenic macrophages co-cultured with Babesia rodhaini and Babesia microti infected erythrocytes2005

    • Author(s)
      Hashiguchi-Kato, R., Pham, N. T., Ohmori, T., Tamahara, S., Katayama, N., Shimada, T., Matsuki, N., Ono, K.
    • Journal Title

      J. Protozool. Res. 15

      Pages: 48-56

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identification and cornification-related gene expression of canine keratinocyte differentiation-associated protein, Kdap.2005

    • Author(s)
      Yagihara, H. et al.
    • Journal Title

      Vet.J. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characterization of cDNA and the genomic sequence encoding canine neural-cell adhesion molecule, CD56/N-CAM.2005

    • Author(s)
      Bonkobara, M. et al.
    • Journal Title

      Vet.Immunol.Immunopathol. 107

      Pages: 171-176

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Esrtablishment and biological characterization of canine histiocytic sarcoma cell line2005

    • Author(s)
      Ono K.et al.
    • Journal Title

      J.Vet.Med.Sci (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of differenciation for antigen presenting cell line2005

    • Author(s)
      Matsuki N.et al.
    • Journal Title

      J Vet.Med.Sci. (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Isokalation and characterization of cell surface antigen on Babasia spp2005

    • Author(s)
      Matsumoto Y.
    • Journal Title

      J.Vet.Med.Sci. (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Serum interleukin-12 1evels and splenic helper T cell subpopulation in Babesia rodhaini inoculated mice preimmunized with Babesia microti.2004

    • Author(s)
      Hashiguchi-Kato, R. et al.
    • Journal Title

      J. Protozool. Res. 14

      Pages: 50-54

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Primary hepatic plasma cell tumor in a dog.2004

    • Author(s)
      Aoki, M. et al.
    • Journal Title

      J. Vet. Med. Sci. 66

      Pages: 445-447

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Serum interleukin-12 levels in mice infected with Babesi microti and Babesia rodhaini2004

    • Author(s)
      Hashiguchi-Kato, R., Pham, N. T., Ohmori, T., Tamahara, S., Tomihari, M., Shimada, T., Matsuki, N., Ono, K.
    • Journal Title

      J Protozool. Res. 14

      Pages: 50-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Serum interleukin-12 levels and splenic helper T cell subpopulation in Babesia rodhaini inoculated mice preimmunized with Babesi microti2004

    • Author(s)
      Hashiguchi-Kato, R., Pham, N. T., Ohmori, T., Tamahara, S., Tomihari, M., Shimada, T., Matsuki, N., Ono, K.
    • Journal Title

      J Protozool. Res. 14

      Pages: 43-49

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Primary hepatic plasma cell tumor in a dog2004

    • Author(s)
      Aoki, M., Kim T., Shimada, T., Kuwamura, M., Ohashi, F.
    • Journal Title

      J. Vet. Med. 66

      Pages: 445-447

    • NAID

      110003886426

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi