| Project/Area Number |
10470243
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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 |
General surgery
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
GOTOH Mitsukazu Fukushima Medical University, Dpt. of Surgery I, Prof., 医学部, 教授 (50162160)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHINO Yasuaki Fukushima Medical University, Dpt. of Surgery I, Medical Staff, 医学部, 助手 (50285045)
SAITO Takuro Fukushima Medical University, Dpt. of Surgery I, Medical Staff, 医学部, 助手 (20305361)
ABE Tsuyoshi Fukushima Medical University, Dpt. of Surgery I, Associate Prof., 医学部, 講師 (90212547)
HOSHINO Yutaka Fukushima Medical University, Dpt. of Surgery I, Medical Staff, 医学部, 助手 (30295414)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1998: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | Islet transplantation / mouse / rejection / anergy / adhesion molecule / regulatory cell / cell transfer / monoclonal antibody / 混合リンパ球反応 / 抗LFA-1抗体 / 抗ICAM-1抗体 / 抗B7-1抗体 / 抗B7-2抗体 / 生着延長効果 |
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| Research Abstract |
Induction of antigen-specific unresponsiveness to grafts is the ultimate goal for organ transplantation. It has been shown that anergic T cells generated in vivo can be transferred as suppresser cells. Anergic cells generated in vitro have never been successfully used to prevent allograft rejection in vivo. We examined whether anergic cell generated in vitro by blocking CD28/B7 costimulatory pathway can suppress allograft rejection in vivo. Anergic T cells were generated in vitro by the addition of anti-B7-1 and anti-B7-2 mAbs to primary MLR consisting of C57BL/6(B6) splenocytes as responder and irradiated BALB/c splenocytes as stimulator. We tested the ability of these cells to respond to various stimuli and to suppress alloreactive T cell responses in vitro. For in vivo studies, 4 x 10ィイD17ィエD1 anergic cells were injected intravenously immediately after transplantation of BALB/c islets under the renal subcapsular space of streptozotocin-induced diabetic and 2.5-Gy X-irradiated B6 mice. Anergic cells treated with both mAbs in the primary MLR did not proliferate in secondary MLR against BALB/c and third-party C3H/He stimulators. The cells also failed to respond to immobilized anti-CD3 mAb, although they proliferated in response to Con A or PMA + ionomycin. The anergic state was reversed by the addition of exogenous IL-2. Furthermore, these cells suppressed the proliferation of naive B6 T cells against either the same (BALB/c) or third-party (C3H/He) stimulator cells. In in vivo studies, irradiated B6 mice rejected BALB/c islet allografts acutely with a MST of 27.0+/-3.8 days, while two of six animals injected with the anergic cells accepted the allografts indefinitely (>100 days) with a MST of 52.0+/-38.2 days. Anergic cells generated in vitro by blocking CD28/B7 costimulatory pathway suppress islet allograft rejection after adoptive transfer. This procedure might be clinically useful for promoting allograft survival.
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