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STUDY OF XENO-THYMIC TRANSPLANTATUON FOR XENO-GRAFT

Research Project

Project/Area Number 10671235
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

MORIMOTO Takeshi  AICHI CANCER CENTER, RESEARCH INSTITUTE, RESARCHER, 研究所, 研究員 (70182269)

Co-Investigator(Kenkyū-buntansha) TAGUCHI Osamu  AICHI CANCER CENTER, DIVISION OF MOLECULAR PATHOLOGY, SECTION HEAD, 分子病態学部, 室長 (00142167)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsTHYMUS / XENO-RAFT / NUDE MOUSE / RAT / OVARY / THYROID / 胸腺内臓器移植 / T細胞 / ブタ / ウシ / ウサギ / モルモット
Research Abstract

Reconstitution of T cell functions in athymic BALB/c nude mice was investigated after transplantation of embryonic thymus grafts under the renal capsule (TG nude mice). Thymi were obtained from mice, rats, rabbits, hamsters, guinea pigs, swine and cows. All of the grafted thymi grew and formed proper thymic structure with host CD90 positive cells. The TCRβ expression pattern of the lymphocytes in the grafted thymi was quite similar to that of normal mouse thymocytes. Sufficient CD4 positive populations were observed in the peripheral lymphoid organs of all groups of TG nude mice. Plaque-forming cell assay revealed that the TG nude mice had acquired considerable helper T cell functions. Skin grafts from syngeneic mice and thymic donor rat strains were accepted, whereas those from allogeneic mice and the rats of other strains were vigorously rejected. Histological and serological studies, however, showed multiple organ-licalized inflammatory diseases in TG nude mice of all xenogeneic thymus groups, but not with syngeneic or allogeneic thymi. The organs affected were thyroid, the lacrimal, submandibular and sublingual glandsm, the eyes, stomach and ovaries. The incidence of lesions was variable depending on the species of origin of the grafted thymus. Development of autoimmune diseases in TG nude mice was prevented by a single injection of splenic CD4 positive cells from normal BALB/c mice. These results together suggested that the microenvironment of grafted thymi, even if xenogeneic, is able to educate host T cell precursors. However, this reconstitution of function does not always induce tolerance to certain autoantigens, resulting in development of multiple autoimmune lesions.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Igakura,T. et al: "A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis."Dev.Biol.. 194. 152-165 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeuchi,M. et al: "Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization."Eur.J.Immunol.. 28. 1578-1586 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kagami,Y. et al: "Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma of CD2+, sCD3- CD3ε+, CD56+ phenotype and associated with the Epstein-Barr virus."Brit.J.Haematol.. 103. 669-677 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohno,K. et al: "Successful transfer of localized autoimmunity with positively selected CD4^+ cells to scid mice lacking functional B cells."Autommunity. 29. 103-110 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yasumura,M. et al: "Protective effects of 5, 6, 7, 8-tetrahydroneopterin against x-ray radiation injury in mice."Biochim.Biophys.Acta.. 1453. 378-384 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishiguro,K. et al: "Syndecan-4 expression is associated with follicular atresia in mouse ovary."Histochem.Cell.Biol.. 112. 25-33 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishigaki-Maki,K. et al: "Autoimmune diseases developed in athymic nude mice grafted with embryonic thymus of xenogeneic origin."Eur.J.Immunol.. 29. 3350-3359 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi,Y. et al: "A binding site for transcription factor Grainyhead/NTF-1 contributes to the regulation of the Drosophila proliferating cell nuclear antigen gene promoter."J.Biol.Chem.. 274. 35080-35088 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morimoto,T. et al: "Transplantation of xenogeneic embryonic thymus to athymic nude mice induces acquisition of distorted immunity."Transpl.Proc.. 32. 956-957 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohno,K. et al: "Characterization of a Drosophila homologue of the human myelodysplasia/myeloid leukemia factor(MLF)."Gene. 260. 133-143 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kontani,K. et al: "Autologous dendritic cells or cells expressing both B7-1 and MUC 1 can rescue tumor-specific cytotoxic T lymphocytes from MUC 1-mediated apoptotic cell death."J.Leuko.Biol.. 68. 225-232 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Igakura, T., Kadomatsu, K., Kaname, T., Muramatsu, H., Fan, Q.-W., Miyauchi, T., Toyama, Y., Kuno, N., Yuasa, S., Takahashi, M., Senda, T., Taguchi, O., Yamamura, K., Arimura, K.and Muramatsu, T.: "A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis."Dev. Biol.. 194. 152-165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeuchi, M., Kezuka, T., Inoue, H., Sakai, J., Usui, , M., Takahashi, T.and Taguchi, O.: "Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization."Eur. J.Immunol.. 28. 1578-1586 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kagami, Y., Nakamura, S., Suzuki, R., Iida, S., Yatabe, Y., Okada, Y., Kobayashi, T., Tsurumi, T., Seto, M., Ogura, M., Taguchi, O.and Morishima, Y.: "Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma of CD2+, sCD3-, CD3_ε+, CD56+ phenotype and associated with the Epstein-Barr virus."Brit. J.Haematol.. 103. 669-677 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohno, K., Takahashi, T., Maki, K., Ueda, M.and Taguchi, O.: "Successful transfer of localized autoimmunity with positively selected CD4^+ cells to scid mice lacking functional B cells."Autoimmunity. 29. 103-110 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yasumura, M., Morimoto, T., Takagi, M., Hirose, H.and Taguchi, O.: "Protective effects of 5,6,7,8-tetrahydroneopterin against x-ray radiation injury in mice."Biochim. Biophys. Acta. 1453. 378-384 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishiguro, K., Kojima, T., Taguchi, O., Saito, H., Muramatsu, T.and Kadomatsu, K.: "Syndecan-4 expression is associated with follicular atresia in mouse ovary."Histochem. Cell. Biol.. 112. 25-33 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishigaki-Maki, K., Takahashi, T., Ohno, K., Morimoto, T., Ikeda, H., Takeuchi, M., Ueda, M.and Taguchi, O.: "Autoimmune diseases developed in athymic nude mice grafted with embryonic thymus of xenogeneic origin."Eur. J.Immunol.. 29. 3350-3359 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashi, Y., Yamagishi, M., Nishimoto, Y., Taguchi, O., Matsukage, A.and Yamaguchi, M.: "A binding site for transcription factor Grainyhead/NTF-1 confributes to the regulation of the Drosophila proliferating cell nuclear antigen gene promoter."J.Biol. Chem.. 274. 35080-35088 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morimoto, T., Nishigaki-Maki, K., Ohno, K., Ikeda, H., Takeuchi, M., Ueda, M., Takahashi, T.and Taguchi, O.: "Transplantation of xenogeneic embryonic thymus to athymic nude mice induces acquisition of distorted immunity."Transpl. Proc.. 32. 956-957 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohno, K., Takahashi, Y., Hirose, F., Inoue, Y.H., Taguchi, O., Nishida, Y., Matsukage, A.and Yamaguchi, M.: "Characterization of a Drosophila homologue of the human myelodysplasia/myeloid leukemia factor (MLF)."Gene. 260. 133-143 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kontani, K., Taguchi, O., Narita, T., Hiraiwa, N., Sawai, S., Hanaoka, J., Ichinose, M., Tezuka, N., Inoue, S., Fujino, S.and Kannagi, R.: "Autologous dendritic cells or cells expressing both B7-1 and MUC 1 can rescue tumor-specific cytotoxic T lymphocytes from MUC 1-mediated apoptotic cell death."J.Leuko. Biol.. 68. 225-232 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morimoto,T. et al: "Transplantation of xenogeneic embryonic thymus to athymic nude mice induces acquisition of distorted immunity."Transpl.Proc.. 32. 956-957 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohno,K. et al: "Characterization of a Drosophila homologue of the human myelodysplasia/mycloid leukemia factor (MLF)."Gene. 260. 133-143 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kontani,K. et al: "Autologous dendritic cells or cells expressing both B7-1 and MUC 1 can rescue tumor-specific cytotoxic T lymphocytes form MUC I-mediated apoptotic cell death."J.Leuko.Biol.. 68. 225-232 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohno, K. et al: "Successful transfer of localized autoimmunity with positively selected CD4 cells to scid mice lacking functional B cells"Autoimmunity. 29. 103-110 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasumura, M. et al: "Protective effects of 5, 6, 7, 8-tetrahydroneopterin against x-ray radiation injury in mice"Biochim. Biophys. Acta.. 1453. 378-384 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishiguro, K. et al: "Syndecan-4 expression is associated with follicular atresia in mouse ovary"Histochem. Cell. Biol.. 112. 25-33 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishigaki-Maki, K. et al: "Autoimmune diseases developed in athymic nude mice grafted with embryonic thymus of xenogeneic origin"Eur. J. Immunol.. 29. 3350-3359 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi, Y. et al: "A binding site for transcription factor Grainyhead/NTF-1 contributes to the regulation of the Drosophila proliferating cell nuclear antigen gene promoter"J. Biol. Chem.. 274. 35080-35088 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morimoto, T. et al: "Transplantation of xenogeneic embryonic thymus to athymic nude mice induces acquisition of distorted immunity"Transpl. Proc.. (In press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Igakura,T.et al: "A null mutation in basigin,an immunoglobulin superfamily member,indicates its important roles in peri-implantation development and spermataogenesis" Dev.Biol.194. 152-165 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeuchi,M.et al: "Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization" Eur.J.Immunol.28. 1578-1586 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohno,K.et al: "Successful transfer of localized autoimmunity with positively selected CD4+cells to scid mice lacking functional B cells" Autoimmunity. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasumura,M.et al: "Protective effects of 5,6,7,8-tetrahydroneopterin against X-ray radiation injury in mice" Biochim.Biophys.Act. (in press).

    • Related Report
      1998 Annual Research Report

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

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