| Project/Area Number |
11671169
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
YUKIHIRO Tomita Kyushu Univ, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (90180174)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Takahiro Kyushu Univ.Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (50284500)
西村 陽介 九州大学, 医学部, 助手 (50301338)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | cyclophosphamide / busulfan / donor specific toleranse / chimerism / drug-induced tolerance / B細胞 / キメラ / 免疫寛容 / 閉塞性冠動脈病変 / Cycolphosphamide |
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| Research Abstract |
A pure method of drug cyclophosphamide (CP) plus busulfan (BU))-induced skin allograft tolerance in mice that can regularly overcome fully H-2 mismatched barriers in mice has been established. The components of the method are intravenous administration of 1x108 allogeneic spleen cells on day O, intraperitoneal injection of 200 mg/kg CP and 25 mg/kg BU on day 2, and intravenous injection of T cell-depleted 1x107 bone marrow cells, from same donor on day 3. Recipient B10 (H-2b ; IE-) mice prepared with this conditioning developed donor (B10.D2 (H-2d ; IE+))-specific tolerance, and long-lasting survival of skin allografts was shown in almost of the recipient mice. In the tolerant B10 mice prepared with new conditioning, stable multilineage mixed chimerism was observed permanently, and IE-reactive Vb11+T cells were reduced in the periphery as seen in untreated B10.D2 mice. The specific tolerant state was confirmed by the specific abrogation against donor antigens in the assays of CTL activity and MLR, and donor B10.D2 specific acceptance in the second set skin grafting.
These results demonstrated that the limitation of standard protocol of CP-induced tolerance, which have been reported by us since 1984, can be overcome by the additional treatments with myelosuppressive drug BU followed by 1x107 T cell-depleted donor bone marrow cells. To our knowledge, this is the first report to induce allograft tolerance with a short course of the antigen plus immunosuppressive drug treatment without any kinds of mAbs (pure drug-induced tolerance).
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