2005 Fiscal Year Final Research Report Summary
A study for the induction of transplantation tolerance using adenovirus expressing PD-1 ligands and application to myoblast transplantation into infarcted hearts.
| Project/Area Number |
15390415
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
SAKAKIDA Satoru Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90311753)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAKURA Ryota Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)
SAWA Yoshiki Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00243220)
FUKUSHIMA Norihide Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (30263247)
MATSUMIYA Goro Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (20314312)
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| Project Period (FY) |
2003 – 2005
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| Keywords | immunological tolerance / transplantation / co-stimulatory molecules |
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| Research Abstract |
We have generated five new recombinant adenovirus that express mouse B7.1, B7.2, PDL-1, PDL-2, or ICOS ligand and used them to study immunoregulatory functions of the proteins on alloimmune responses. The results are summarized as below.
1. Introductions of cDNA for all the molecules were successful. The generated E1/E3 defective non-reproductive recombinant adenovirus woll become new research resources uniquely generated by this project.
2. The generated adenovirus could be easily infected to adherent mammalian cells including cultured skeletal myoblasts and HeLa cells and effectively induced surface expression of the introduced molecules. However, it was difficult to infect and induce the expression on non-adherent cells such as those of lymphoid origin, even if the cells from the Coxsackie-Adenovirus receptor transgenic animals were used.
3. Threfore, it was impossible to test the possibility if the generated virus could improve the efficacy of the ability to induce allogeneic tolerance by the intravenous presensitization of hosts with allogeneic lymphoid cells. Alternatively, we have tested the immunomodulatory functions of the molecules in vivo by measuring anti-adenovirus antibodies by hosts which had been infected with the generated recombinant virus. As a results, PDL-1 but not PDL-2 was suggested to have immunosuppressive effects on anti-virus immune reaction. The effect, however, was weaker if it was compared to that observed by the injection of adenovirus expressing CTLA4-Ig, a well-known immunosuppressant and a blocker of CD28-B7 interactions.
4. Autologous skeletal myoblasts implantation was established as a possible therapeutic method to improve failed cardiac functions of infarcted rat hearts. It would be a strategy to treat myocardial infarction in future that allogeneic skeletal myoblasts will be modified to express PDL-1 on their surface and transplanted on the impaired hearts as the sheet to restore the cardiac functions.
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