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Physiological and cell biological studies on dendritic cells

Research Project

Project/Area Number 10044268
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

INABA Kayo  Kyoto University, Graduated School of Science, Associated Professor, 大学院・生命科学研究科, 教授 (00115792)

Co-Investigator(Kenkyū-buntansha) 稲葉 カヨ  京都大学, 大学院・生命科学研究科, 教授 (00115792)
SHORTMAN Ken  ウォルター, エリザホール医学研究所・免疫部門, 部長
STEINMAN Ral  ロックフェラー大学, 細胞生理免疫学部門, 教授
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥4,400,000 (Direct Cost: ¥4,400,000)
Keywordsdendritic cells / antigen-presentation / antigen processing / MHC class II / immune response / functional maturation / T cell activation / 細胞間相互作用 / クロスプライミング / 細胞分化 / 食作用能
Research Abstract

Antigen uptake, processing and presentation by dendritic cells (DCs) have become amenable to cell biological approaches. The critical events occur in DCs that are undergoing development and maturation in response to inflammatory stimuli. The aim of this project is to define developmental stages and to elucidate regulatory mechanisms of antigen processing in immunostimulatory dendritic cells. The following results are obtained.
1) DCs ate unusually efficient at forming MHC-peptide complexes from phagocytosed cells, some 1-10 thousand times more efficiently than an exposure to preprocessed peptide. A comparable phenomenon is observed in vivo when short-lived migratory DCs migrate via afferent lymphatics to the T cell areas of the lymph nodes.
2) After phagocytosing injected microspheres, about 25% of inflammatory monocytes migrated to the T area of draining node, where they expressed dendritic cell-restricted markers and high levels of costimulatory molecules.
3) Fractalkine/neurotactin and … More MDC are isolated from mouse bone marrow-derived DC cDNA libraries by the signal sequence trap method. Both chemokines are expressed by DC differentiated from bone marrow precursors cells in vitro and mature DCs from tissues, and constitutively produced by DCs in T area to attract T cells.
4) Based on the relative expression of CD11c and CD1a, we have identified three fractions of DCs in human peripheral blood. A major population expressing CD1a and CD11c is demonstrated to be immediate precursors of epidermal Langerhans cells. A minor fraction (CD1a-CD11c-) is identified as plasmacytoid T cells, which are supposed to be lymphoid-lineage DCs.
5) Immature dendritic cells internalize antigens into lysosomal compartments rich in MHC II molecules. The capacity of MHC-rich lysosomes to mediate the formation of MHC II-peptide complexes is strictly controlled during dendritic cell differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of ligands for the T cell receptor. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Inaba,K.: "Transport peptide-MHC class II complexes in developing dendritic cells"Science. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "The formation of immunogenic MHC class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli"J. Exp. Med.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Dendritic cell at a DNA vaccination site express an encoded influenza nucleoprotein and prime CD8+ cytolytic lymphocytes upon adoptive transfer"Int. Immunol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Experimental autoimmune thyroiditis induced by thyroglobulin-pulsed dendritic cells"Autommunoty. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Efficient Induction of peptide specific cytotoxic T lymphocytes LPS activated spleen cells"Microbiol. Immunol.. 44(2). 123-133 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Can the capture of apoptotic cells by dendritic lead to tolerance?"J. Exp. Med.. 191(2). 414-416 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo"Immunity. 11(6). 753-761 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Cdla+/CDllc+ subset of human blood dendritic cells is a direct precursor of Langerhans cells"J. Immunol.. 163(3). 1409-1419 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Myeloid dendritic cells"J. Leukocyte Biol.. 66. 205-208 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Fractalkine and macrophage-derived chemokine (MDC) : T cell attractive chemokines expressed in T cell area dendritic cells"Eur. J. Immunol.. 29(6). 1925-1932 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Antigen capture, processing, and presentation by dendric cells: Recent cell biological studies"Human Immunol.. 60. 562-567 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Presence of B cell progenitors in the thymus"Mol. Biol. Hematopoiesis. 6. 65-70 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba,K.: "Efficient presentation of phagocytosed cellular fragments of the MHC class II products of dendritic cells"J. Exp. Med.. 188(11). 2163-2173 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Turley, S., Inaba, K., Garrett, W., Ebersold,, M. Steinman, R. M. and Mellman, I.: "Transport of peptide-MHC class II complexes in developing dendritic cells"Science. (in press.). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba, K., Turley, S., Iyoda, T., Yamaide, F., Shimoyama, S., Reis e Sousa, C., Germain, R., Mellman, I. and Steinman, R. M.: "The formation of immunogenic MHC class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli."J. Exp. Med.. (in press.) (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Bot, A., Stan A.-C., Inaba, K., Steinman, R. M. and Bona, C.: "Dendritic cell at a DNA vaccination site express an encoded influenza nucleoprotein and prime CD8ィイD1+ィエD1 cytolytic lymphocytes upon adoptive transfer."Int. Immunol.. (in press.). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Watanabe, H., Inaba, M., Adachi, Y., Sugiura, K., Hisha, H., Igichi, T., Ito, T., Yasumizu, R., Inaba, K., Yamashita, T. and Lkehara, S.: "Experimental autoimmune thyroiditis induced by thyroglobulin-pulsed dendritic cells."Autoimmunity. (in press.). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kakugawa, K., Udaka, K., Nakashima K., Inaba, K., Oka, Y., Sugiyama, H., Tamamura, H. and Yamagishi, H.: "Efficient Induction of peptide specific cytotoxic T lymphocytes by LPS activated spleen cells."Microbiol. Immunol.. 44(2). 123-133 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Steinman, R. M., Turley, S., Mellman, I. and Inaba, K.: "Can the capture of apoptotic cells by dendritic cells lead to tolerance?"J. Exp. Med. 191(2). 414-416 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Randolph G. J., Inaba, K., Robbiani D. F., Steinman, R. M. and Muller, W. A.: "Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo."Immunity. 11(6). 753-761 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito T., Inaba M., Inaba K., Toki, J., Sogo T., Iguchi T., Adachi, Y., Yamaguchi, K., Amakawa, R., Valladeau, J., Saeland, S., Fukuhara, S. and Ikehara S.: "A CDlaィイD1+ィエD1/CDllcィイD1+ィエD1 subset of human blood dendritic cells is a direct precursor of Langerhans cells."J. Immunolo.. 163(3). 1409-1419 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Steinman, R. M., and Inaba. K.: "Myeloid dendritic cells."J. Leukocyte Biol.. 66. 205-208 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kanazawa, No., Nakamura, T., Tashiro, K., Muramatsu, M., Morita, K., Yoneda, K., Inaba, K.: "Imamura, S. and Honjo, T. Fractalkine and macrophage-derived chemokine (MDC) : T cell attractive chemokines expressed in T cell area dendritic cells."Eur. J. Immunol.. 29(6). 1925-1932 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Steinman, R. M., Inaba, K., Turley, S., Pierre, P. and Mellman, I.: "Antigen capture, processing, and presentation by dendritic cells : Recent cell biological studies."Human Immunol.. 60. 562-567 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba, M., Mori, S-I., Sugiura A, Feng, B., Ito, M., Inaba, K. and Ikehara S: "Presence of B cell progenitors in the thymus."Mol. Biol. Hematopoiesis. 60. 65-70 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inaba, K., Turley, S., Yamaide, F., Iyoda, T., Mahnke, K., Inaba, M., Pack, M., Subklewe, M, Sauter, B., Sheff, D., Albert, M., Bhardwaj, N., Mellman,I and Steinman, R.M.: "Efficient presentation of phagocytosed cellular fragments on the MHC class II products of dendritic cells"J. Exp. Med.. 188(11). 2163-2173 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Turley S.: "Transport of peptide-MHC class II complexes in developing dendritic cells"Science. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inaba K.: "The formation of immunogenic MHC class II-peptide ligands in lysosomal compartments of dendritic cells in regulated by inflammatory stimuli"J. Exp. Med.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Bot A.: "Dendritic cell at a DNA vaccination site express an encoded influenza nucleoprotein and prime CD8^+ cytolytic lymphocytes upon adoptive transfer"Int. Immunol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe H.: "Experimental autoimmune thyroiditis induced by thyroglobulin-pulsed dendritic cells"Autoimmunoty. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Steinman R.M.: "Can the capture of apoptotic cells by dendritic cells lead to tolerance?"J. Exp. Med.. 191(2). 414-416 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kakugawa K.: "Efficient Induction of peptide specific cytotoxic T lymphocytes by LPS actibated spleen cells"Microbiol. Immunol.. 44(2). 123-133 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Randolph G.J.: "Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo"Immunity. 11(6). 753-761 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito T.: "Cdla^+/CD11c^+ subset of human blood dendritic cells is a direct precursor of Langerhans cells"J. Immunol.. 163(3). 1409-1419 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Steinman R.: "Myeloid dendritic cells"J. Leukocyte Biol.. 66. 205-208 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kanazawa N.: "Fractalkine and macrophage-derived chemokine (MDC) : T cell attractive chemokines expressed in T cell area dendritic cells"Eur. J. Immunol.. 29(6). 1925-1932 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Steinman R.M.: "Antigen capture, processing, and presenatation by dendritic cells: Recent cell biological studies"Human Immunol.. 60. 562-567 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inaba,K.: "Efficient presentation of phagocytosed cellular fragments on the MHC class II products of dendritic cells." J.Exp.Med.188. 2163-2173 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Steinman,R.M.: "Myeloid dendritic cells." J.Leukocyte Biol.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanazawa,N.: "Fractalkine and macrophage-derived chemokine(MDC):T cell attractive chemokines expressed in T cell area dendritic cells." Eur.J.Immunol.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Steinman,R.M.: "Antigen capture,processing,and presentation by dendritic cells:Recent cell biological studies." Human Immunol.(in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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