Approaches to the clinical application of donor-specific tolerance in living donor organ transplantation.

供者特异性耐受在活体器官移植中的临床应用方法。

基本信息

批准号：
14207049
负责人：
KITAJIMA Masaki
金额：
$ 32.61万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

(1)Alloantigen or allopeptide can induce hyporesponsiveness to fully mismatched cardiac allografts when delivered intratracheally or orally.(2)Alloantigen or allopeptide can generate regulatory cells when delivered intratracheally.(3)The population of regulatory cells contains regulatory T cells and regulatory dendritic cells.(4)The regulatory T cells and regulatory dendritic cells can suppress rejection of allogeneic heart grafts.(5)The suppression by regulatory T cells and regulatory dendritic cells is donor specific.(6)Intratracheal delivery of alloantigen combined with anti-CD4 mAb or anti-CD40L mAb induces operational tolerance to fully allogeneic cardiac allografts.(7)CD80/86 pathway, signals of THF-family and PD-1 signal are necessary for induction of regulatory cells by intratracheal delivery of alloantigen, individually.(8)IL-10 is essential for induction of regulatory cells by intratracheal delivery of alloantigen.(9)Mycophenolate mofetil and Rapamycin work synergistically for induction of regulatory cells, although high dose of Tacrolimus, Azathioprine and Cyclosporine prevent generating regulatory cells.(10)Histamine 2 receptor antagonist, serotonin receptor antagonist, ursodeoxycholic acid, MCI-186 (free radical scavenger) and anti-thrombin III can generate regulatory cells.(11)The fraction of regulatory T cells is CD4^+CD25^+CTLA4^+ in our model.(12)The number of CD4^+CD25^+CTLA4^+ cells decreased before rejection episode in preliminary clinical study.

(1)同种抗原或同种肽在气管内或口服递送时可诱导完全错配的同种异体心脏移植物的低反应性。(2)同种抗原或同种肽在气管内递送时可产生调节细胞。(3)调节细胞群包含调节性T细胞和调节性树突状细胞(4)调节性T细胞和调节性树突状细胞可以抑制同种异体心脏移植物的排斥反应。(5)调节性T细胞和调节性树突状细胞的抑制作用调节性树突状细胞具有供体特异性。(6)气管内递送同种异体抗原与抗CD4 mAb或抗CD40L mAb联合诱导对完全同种异体心脏同种异体移植物的操作耐受。(7)CD80/86通路、THF家族信号和PD- 1 个信号对于通过气管内递送同种抗原单独诱导调节细胞是必需的。(8)IL-10 对于通过气管内递送诱导调节细胞是必需的(9) 吗替麦考酚酯和雷帕霉素协同作用诱导调节细胞，尽管高剂量的他克莫司、硫唑嘌呤和环孢菌素会阻止调节细胞的产生。(10) 组胺 2 受体拮抗剂、血清素受体拮抗剂、熊去氧胆酸、MCI- 186（自由基清除剂）和抗凝血酶III可以产生调节性(11)在我们的模型中，调节性T细胞的比例是CD4^+CD25^+CTLA4^+。(12)在初步临床研究中，CD4^+CD25^+CTLA4^+细胞的数量在排斥发生之前减少。