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Role of co-stimulatory signal in long-term acceptance of human kidney allogrfts.

共刺激信号在人肾同种异体移植物长期接受中的作用。

基本信息

批准号：
13671646
负责人：
ONO Yoshinari
金额：
$ 0.7万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

To evaluate the role of co-stimulatory signal in long-term human kidney allograft acceptance, CD 2, CD 11a and CD 28 expression on peripheral lymphocytes of human kidney transplant patients were examined in 67 kidney transplant patients, 14 healthy volunteers and 10 hemodialysis patients. Only CD 28 was remarkably depressed in the kidney transplant patients, which was significantly correlated with the duration of graft survival. In age matched healthy volunteers and hemodialysis patients did not have depressed expression of co-stimulatory antigens. Depressed CD28 was induced mainly on CD4 positive T cells. The CD28-negative CD 4-positive T cell did not express CD 25, CD69, V alpha 24 nor CTLA-4. RT-PCR and southern blotting analysis for repertoire of the V beta chain indicated remarkable deviation in the CD28-negative CD 4-positive T cell. Also, it had elevated expression of INF-gammer and TGF-beta 1, but not IL-4 and IL-10. In MLC study between kidney transplant patients, donors and third party, donor specific suppression was observed in patients with the more CD28-negative CD 4-positive T cells. In prospective 3 year-survey of the rate of CD28-negative CD 4-positive T cell/CD 4-positive T cell in 74 long-term kidney transplant patients, it was lower in the recipients with chronic rejection.In conclusion, the CD28-negative CD 4-positive T cell might be induced by continuous stimulation of donor antigens and might play a significant role in suppression of rejection.

为探讨共刺激信号在人肾移植长期接受性中的作用，对67例肾移植患者、14例健康志愿者和10例血液透析患者外周血淋巴细胞CD2、CD11a和CD28的表达进行了检测。肾移植患者中仅CD28显著降低，与移植肾存活时间显著相关。在年龄匹配的健康志愿者和血液透析患者中，共刺激抗原的表达没有受到抑制。CD28表达下调主要发生在CD4阳性T细胞上。CD28阴性的CD4阳性T细胞不表达CD25、CD69、Vα24，也不表达CTLA-4。RT-PCR和Southern blotting对Vβ链的分析表明，CD28阴性的CD4阳性T细胞有明显的偏离。干扰素-γ和转化生长因子-β1表达增加，而IL-4和IL-10表达无明显变化。在肾移植患者、供者和第三方之间的MLC研究中，CD28阴性的CD+T细胞较多的患者观察到供者特异性抑制。在对74例长期肾移植患者的3年前瞻性调查中，CD28阴性的CD4+T细胞/CD4+T细胞比率在慢性排斥反应受者中较低。结论：CD28阴性的CD4阳性T细胞可能是供者抗原持续刺激诱导的，在抑制排斥反应中可能起重要作用。