The induction of donor-specific transplantation tolerance in pancreas transplantation combined with spleen in rat

大鼠胰脏联合移植诱导供者特异性移植耐受

• 批准号: 16591262
• 负责人: SUGITANI Atsushi
• 金额: $ 2.3万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591262/
• 关键词: regulatory T cell; transplantation tolerance; pancreas transplantation; spleen

Aim : To investigate the role of spleen and regulatory T cell for pancreas transplantation.Method : After induction of diabetes mellitus by streptozotocin, spleen and/or pancreaticoduodenal transplantation (S/PTx or PTx) into the peritoneal cavity was performed using a modification of Lee's method. Graft survival was compared in isograft (Lew to Lew), allograft (DA to Lew) and allograft with tacrolimus induction (1mg/kg/day for 4days) groups. The rate of CD25+CD4+ T cell and the Foxp3 expression in peripheral blood (PB), recipient spleen (RS) and donor spleen (DS) were examined using Flowcytometry and RT-PCR, respectively. The specimen was obtained from RS, DS, and graft pancreas for histological examination on day7.Results : Isotransplanted S/PTx (n=4) and PTx (n=4) were both survived longer than 100days. Both allotransplanted S/PTx (n=6) and PTx (n=6) without tacrolimus rejected the graft on 12.3±2.7d, 11.7±2.9d, respectively. S/PTx (n=6) with tacrolimus survived for 22.8±7.9d, and PTx (n=6) with tacrolimus survived for 13.5±3.7d (p=0.0069). Rejected S/PTx grafts (n=5) showed that 1)CD25+CD4+T cells were dominant in PB, RS and DS, 2) Donor derived CD25+CD4+T cells disappeared after 7days. Survived S/PTx grafts (n=5) showed that 1)donor CD25+CD4+T cells remained in PB, RS and DS over 7days, 2)the rate of Foxp3 expression was in both RS and DS on day7 compared with Rejected graft (p=0.028). There were more lymphocyte infiltration and reduction in white pulp in RS and DS.Conclusion : The pancreas graft survived longer by combined spleen transplantation and a short course of calcineurin inhibitor. Donor derived regulatory T cells (Foxp3 and CD25/4 cells) existing in both recipient and donor spleen would lead micro-chimerism and prolonged survival.

目的：探讨脾脏和调节性T细胞在胰腺移植中的作用。方法：应用链脲佐菌素诱导糖尿病后，采用改良的Lee方法进行脾脏和（或）胰十二指肠腹腔移植（S/PTx或PTx）。比较同种异体移植物（Lew to Lew）、同种异体移植物（DA to Lew）和同种异体移植物诱导他克莫司（1mg/kg/d，连用4d）组的移植物存活率。采用流式细胞术和RT-PCR分别检测外周血（PB）、受体脾（RS）和供脾（DS）中CD25+CD4+ T细胞率和Foxp3的表达。取RS、DS和移植胰腺标本，于第7天进行组织学检查。结果：同位移植的S/PTx （n=4）和PTx （n=4）存活时间均超过100天。同种异体移植的S/PTx （n=6）和未使用他克莫司的PTx （n=6）分别在12.3±2.7d和11.7±2.9d出现排异反应。S/PTx （n=6）联合他克莫司的生存期为22.8±7.9d, PTx （n=6）联合他克莫司的生存期为13.5±3.7d （p=0.0069）。排斥S/PTx移植物（n=5）显示1)CD25+CD4+T细胞在PB、RS和DS中占主导地位，2)供体来源的CD25+CD4+T细胞在7天后消失。存活的S/PTx移植物（n=5）表明：1)供体CD25+CD4+T细胞在PB、RS和DS中存活了7天；2)第7天，RS和DS中Foxp3的表达率与排斥移植物相比（p=0.028）。RS组和DS组淋巴细胞浸润较多，白髓减少。结论：联合脾移植和钙调磷酸酶抑制剂疗程短，胰脏移植成活率高。供体来源的调节性T细胞（Foxp3和CD25/4细胞）存在于受体和供体脾脏中，可导致微嵌合并延长存活时间。

项目成果

ラット膵臓移植モデルにおける脾臓を用いた免疫寛容誘導の可能性

在大鼠胰腺移植模型中使用脾脏诱导免疫耐受的可能性

• 发表时间: 2005
• 期刊: 日本移植学会 40
• 作者: 吉田淳一;田中三津子;杉谷篤;北田秀久;大田守仁;田中雅夫
• 通讯作者: 田中雅夫

Long-Term Results of Tacrolimus Therapy for Renal Transplantation in Patients With Diabetic Nephropathy in Japan (for the Japanese Tacrolimus Study)

他克莫司治疗日本糖尿病肾病患者肾移植的长期结果（针对日本他克莫司研究）

• 发表时间: 2005
• 期刊: Transplantation Proceedings 37
• 作者: A.Sugitani;M.Tanaka;S.Takahara;K.Uchida;H.Yoshimura;K.Takahashi;H.Toma;S.Oshima;T.Sonoda
• 通讯作者: T.Sonoda

Long-Tem Results of Tacrolimus Therapy for Renal Transplantation in Patients With Diabetic Nephropathy in Japan

他克莫司治疗日本糖尿病肾病肾移植患者的长期结果

• 发表时间: 2005
• 期刊: Transplantation Proceedings 37
• 作者: A.Sugitani;M.Tanaka;S.Takahara;K.Uchida;H.Yoshimura;K.Takahashi;H.Toma;S.Oshima;T.Sonoda for the Japanese Tacrolimus Study
• 通讯作者: T.Sonoda for the Japanese Tacrolimus Study

The induction of donor-specific transplantation tolerance in pancreas transplantation combined with spleen in rat

大鼠胰脏联合移植诱导供者特异性移植耐受

• 发表时间: 2005
• 期刊: The Japan Society for Transplantation 40
• 作者: J.Yoshida;M.Tanaka;A.Sugitani;H.Kitada;M.Ota;M.Tanaka
• 通讯作者: M.Tanaka

Long-Term Results of Tacrolimus Therapy for Renal Transplantation in Patients With Diabetic Nephropathy in Japan

他克莫司治疗日本糖尿病肾病肾移植患者的长期结果

• 发表时间: 2005
• 期刊: Transplantation Proceedings 37
• 作者: A.Sugitani;M.Tanaka;S.Takahara;K.Uchida;H.Yoshimura;K.Takahashi;H.Toma;S.Oshima;T.Sonoda for the Japanese Tacrolimus Study
• 通讯作者: T.Sonoda for the Japanese Tacrolimus Study