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Tolerance induction and its mechanism in lung transplantation ― The expression and the role of CTLA-4 molecule

Research Project

Project/Area Number 12671298
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionChiba University

Principal Investigator

SAITOH Yukio  Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (60261905)

Co-Investigator(Kenkyū-buntansha) SAITOH Takashi  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (50205655)
FUJISAWA Takehiko  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80110328)
SEKINE Yasuo  Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (70312957)
馬場 雅行  千葉大学, 大学院・医学研究院, 助教授 (00143305)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordslung transplantation / rat / CTLA-4 / donor specific transfusion / tolerance
Research Abstract

(1) The expressions of CTLA-4 and CD28 in the recipient spleen T cells and these on the recipient spleen T cell surface after donor specific transfusion (DST) from Brown Norway to Fisher 344 rats were investigated by FACS and a confocal laser microscope. CD28 expressed both in and on the T cells in the DST rats as well as untreated rats. On the other hand, although CTLA-4 did not express on the T cell surface before and after DST, intra-cellular expression of CTLA-4 was observed after DST in the 20 % of T cells. This result suggested that DST has some relationship to intra-cellular expression of CTLA-4 in T cells.
(2) DST 7 days before transplantation induced prolongation of graft rejection by pathology. Control group showed grade 4 rejection, while DST group showed grade 1. As a third party, DST from ACI to F344 was performed and BN to F344 lung transplantation was performed. Pathology revealed grade 3 to 4. This suggested that DST was donor specific.
(3) CTLA-4 expression on the surface of graft infiltrating T lymphocytes (GIL) was investigated in a time course by FACS. In an isograft model, CTLA-4 expression was not identified during the study period of 7 days. In an allograft control model, surface expression was observed at the 3^<rd> day postoperatively. This was consistent with the appearance of rejection by pathology. This expression kept until the 7^<th> day. In an allo-DST model, the surface expression was observed at the first day and maintained for 7days. In the spleen T cells, the same phenomenon was observed.
(4) The same phenomenon as (3) was observed in GIL.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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