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

为探讨共刺激信号在人肾移植长期接受中的作用，检测了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CD 2、CD 11 a和CD 2 8的表达。在肾移植患者中，只有CD 28显著降低，这与移植物存活时间显著相关。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降低。抑制的CD 28主要在CD 4阳性T细胞上诱导。CD 28阴性CD 4阳性T细胞不表达CD 25、CD 69、V α 24和CTLA-4。RT-PCR和Southern印迹分析表明，在CD 28阴性的CD 4阳性的T细胞中，V β链的库存在显著的偏差。此外，它具有升高的INF-γ和TGF-β 1表达，但没有IL-4和IL-10。在肾移植患者、供者和第三方之间的MLC研究中，在具有更多CD 28阴性CD 4阳性T细胞的患者中观察到供者特异性抑制。通过对74例长期肾移植患者的3年前瞻性观察，发现慢性排斥反应受者的CD 28-CD 4-阳性T细胞/CD 4-阳性T细胞比值较低，提示CD 28-CD 4-阳性T细胞可能是供者抗原持续刺激所致，在抑制排斥反应中起重要作用。

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.