1995 Fiscal Year Final Research Report Summary
INDUCTION OF TOLERANCE IN KIDNEY TRANSPLANTATION
| Project/Area Number |
06404044
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
OTA Kazuo Tokyo Women's Medical College, the Medical, Professor, 医学部, 教授 (40090659)
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| Co-Investigator(Kenkyū-buntansha) |
KOGA Shoji Tokyo Women's Medical College, the Medical, assistant, 医学部, 助手 (30277123)
HOSHINI Tomoaki Tokyo Women's Medical College, the Medical, Professor, 医学部, 助手 (40246541)
TANABE Kazunori Tokyo Women's Medical College, the Medical, assistant Professor, 医学部, 講師 (80188359)
TOMA Hiroshi Tokyo Women's Medical College, the Medical, assistant, 医学部, 教授 (90075549)
KAWAI Tatsuo Tokyo Women's Medical College, the Medical, assistant Professor, 医学部, 講師 (40186044)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Immunological Tolerance / chimerism / kidney transplantation |
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| Research Abstract |
INTRODUCTION Previously, we reported a non-myeloablative preparative regimen that can induce mixed chimerism and tolerance in non-human primate (Transplantation 59 : 256,1995). This regimen includes non-lethal total body irradiation (TB,1.5GyX2 or 3GyX1) on day-6, thymic irradiation (TI,7Gy) on day-1, anti-thymocyte globulin (ATG) for 3 days (day-3, -2, and -1), donor bone marrow (DBM), splenectomy and a one month course of cyclosporine A (CsA). But the necessity and meanings of TI and splenectomy or minimum dose of TBI have not been clarified.
AIM and METHOD To clarify which treatment is indispensable to induce mixed chimerism and tolerance in this regimen, we examined a modified regimen, which includes 2.3Gy of TBI on day-6 with or without TI,ATG for 3 days, no splenectomy, DBM and 40 days course of CsA.
be administered immediately before transplantation. 3) Multilineage chimerison but not tolerance can be induced without TI 4) Splenectomy is not necessary for either induction of chimerism or tolerance.
RESULTS by the regimen without TI and splenectomy, although monkeys developed chimerism, they rejected kidney allografts on day 41 and 59 soon after CsA discountinuation. By the regimen with TI on day-6, graft survival was longer than without TI,but eventually rejected kidney allografts around day100 (day 97 and 101). By the regimen with TI on day-1, one monkey who developed chimerism surviived over 140 days. MLR examined after day80 revealed donor specific unresponsiveness. But two other monkeys did not develop chimerism by this regimen and rejected kidney on day64 and 61.
CONCLUSION 1) Multilineage chimerism is necessary but not sufficient for the induction of tolerance. 2) 7 Gy of TI is indispensable for the induction of tolerance in our regimen and it should
be performed immediately before transplantation. 3) Any symptoms of GVHD was not observed in monkeys treated with this regimen.
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