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New method for controlling the rejection which are due to the expression suppression of the MHC class II molecule

Research Project

Project/Area Number 13671388
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionDokkyo University School of Medicine

Principal Investigator

MIYOSHI Shinichirou  Cardiothoratic surgery, Professor, 医学部, 教授 (00190827)

Co-Investigator(Kenkyū-buntansha) MINAMI Masato  Osaka University, Assistant, 医学系研究科, 助手 (10240847)
SUGUTA Kazuhiko  Cardiothoratic surgery, Assistant, 医学部, 助手 (40216312)
IKEDA Yasunori  Cardiothoratic surgery, Instructor, 医学部, 講師 (80202901)
OKUMURA Meinoshin  Osaka University, Assistant, 医学系研究科, 助手 (40252647)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsorgan transplantation / transplantation immunity / rejection
Research Abstract

Control of rejection of the graft and evading infection are the essential subjects for successful organ transplantation. Although effective immunosuppressants, including cyclosporine and tacrolimus, have contributed to improvement of the organ transplantation, additional methods for suppression of graft rejection are still required.
The immunological target in organ transplantation is known to be major histocompatability complex (MHC), and in human, especially HLA-DR molecule is supposed to be the most important antigen. In the present study, we tried to develop a new gene therapy method to down-regulate the expression of HLA-DR molecule in the transplanted organs by interfering the function of MHC class II transactivator (CIITA) molecule, a key transcription factor of MHC class II molecules.
CIIA molecule consists of two portions, an amino-terminus site which is essential in activating the promoter of HMC II genes and a carboxylterminus site which binds to other DNA binding proteins. A deletion mutant protein which expresses only the binding domain is supposed to work as a dominant negative mutation and to suppress the expression of MHC II molecules. The DNA product whose sequence corresponds to the binding domain of the CIITA molecule was derived by the method of RT-PCR. The derived DNA product was inserted into the expression vector, and the DNA construct of dominant negative mutation of CIITA was created.
The DNA construct was introduced by electroporation into Raji cells, the B cell line which expresses HLA-DR. Expression of HLA-DR antigen was shown to be significantly suppressed in the stable transfectants.
This newly created construct presumably works to reduce the possibility of rejection by suppressing the HLA-DR expression of the transplanted graft.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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