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The Clonal Analysis of Effector Mechanism in Graft Rejection

Research Project

Project/Area Number 01570710
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionThe University of Osaka

Principal Investigator

SHIRAKURA Ryota  Osaka Univ. First Dept. of Surg Assoc. Prof., 医学部, 助教授 (00116047)

Co-Investigator(Kenkyū-buntansha) ITO Toshinori  Osaka Univ. First Dept. of Surg. Assoc. Prof., 医学部, 助手 (20231152)
NAKATA Seizoh  Osaka Univ. First Dept. of Surg. Assoc. Prof., 医学部, 助手 (50116068)
福嶌 教偉  大阪大学, 医学部附属病院, 医員
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsAcute rejection / Heart transplantation / Graft infiltrating cells / Limiting dilution assay / Cytotoxic T cell precursor frequency / Suppressor / inducer T cell / Interleukin 2 / Cloning / インタ-ロイキニン / 細胞障害性T前駆細胞頻度 / インタ-ロイキン2
Research Abstract

Limiting Dilution Analysis (LDA) is a quantitative method with a high degree of accuracy and an indispensable way for the elucidation of rejection mechanism and tolerance. It is possible to estimate the absolute clonal size of Tcp (T cytotoxic precursor) by calculating the frequency of Tcp[ f (Tcp)]
. The experimental model is a heterotopic heart transplantation in rats. Buffalo (BUF : RT-1^b) rats were used as heart donors and Wistar-Furth (WFu : RT-1^u) rats as recipients. The spleen T cells of untreated rats had a f (Tcp) of 1:2343<plus-minus>591, but the f (Tcp) just before rejecti on increased up to 1/195<plus-minus>123 which was about 12 times as high as that of the untreated rats. However, the allografted WFu rats had a decreased f (Tcp) of 1 : 696<plus-minus>243 after graft rejection.
Thus, the present study concentrated upon the f (Tcp) of graft infiltrating cells (GICs) on day 5 postgrafting during ongoing rejection. The GICs in an allograft showed a remarkably high f (Tcp) of … More 1 : 113 in comparison with a f (Tcp) of 1 : 8584 seen in an isograft. The number of GICs obtained from allografts was (2.1<plus-minus>1.1)x10^7/graft. This was ten times as many as that isolated from isografts. The FACS analysis of GICs-T revealed that the number of percentage in OX19^+ (T), OX8^+ (Tc/s) and W3/25^+ (Th) cells were 70.9%, 64.5% and 25.9%. respectively.
On day 5 postgrafting, the f (Tcp)s of spleen and lymphnode T cells were 1 : 195<plus-minus>123, 1:731<plus-minus>81, respectively. However, the GICs had the highest f (Tcp) of 1:84<plus-minus>53. Therefore, about 1.2% (1/84) of GICs-T cells was the donor specific Tcp on day5 postgrafting during ongoing reje
On the other hand, the GICs also had T cells which could suppress the proliferative response of Mixed Lymphocyte Culture (MLC) in a donor specific manner. We could make some clones from the GICs on day 5 transplantation. The surface markers of these clones were Ox19^+ (T), W3/25^+ (Th),OX8^- (Ts/c), and OX22^+ (LCA). These clones could suppress the MLC response in a donor specific manner.
Therefore, it is suggested that there might be a regulation mechanism by the T cells which could suppress the unlimited proliferation of donor antigen specific Tc cells in the graft during ongoing rejection on day 5 postgrafting. Less

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] T.Ito et.al: "Frequency of T cytotoxce cells correlates with the immune Atatus in organ allogroft recipients" Transplant.Proc.21. 3282-5 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 伊藤 寿記: "ラット心移植における細胞傷害性T細胞の解析 ー細胞傷害性T前駆細胞頻度からみた急性拒絶反応の制御機構ー" 大阪大学医学会雑誌. 42. 631-643 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 伊藤 寿記他6名: "ラット移植モデルにおける細胞傷害性T細胞の解析 ー2.限界希釈法によるラット細胞傷害性T前駆細胞頻度の測定ー" 日本移植学会誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Ito et al: "Frequency of T cytotoxic cells correlates with the immune status in organ allograft recipients." Transplant Proc. 21. 3282-5 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Ito: "Analysis of cytotoxic T cell in rat heart transplantation -Regulation mechanism of acute rejection estimated by frequency of cytotoxic T cell precursor-" Medical J. of Osaka Univ. 42. 631-40 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Ito et al: "Analysis of cytotoxic T cell in rat heart transplantation 2. -The measurement of cytotoxic T cell precursor frequency by limiting dilution assay." Jap. J. of Transplantation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 伊藤 寿紀: "ラット心移殖における細胞傷害性T細胞の解析ー細胞傷害性T前駆細胞頻度からみた急性拒絶反応の制御機構ー" 大阪大学医学会雑誌. 42. 631-640 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 伊藤 寿紀,他6名: "ラット移殖モデルにおける細胞傷害性T細胞の解析ー2.限界希釈法によるラット細胞傷害性T前駆細胞頻度の測定ー" 日本移殖学会誌.

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Ito: "Freguency of Tcylotoxic cells correlates with the immune status of organ allograft reirpients" Transplantation Proceediugs. 21. 3282-3285 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 伊藤寿記: "急性拒絶反応時のラット脾臓より得られたサプレッサ-T細胞クロ-ンの性状について" 移植.

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2017-03-24  

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