Regulatory CD25+T cells in human kidney transplant recipients
Regulatory CD25+T cells in human kidney transplant recipients
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DOI：
10.1097/01.asn.0000057540.98231.c1
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发表时间：
2003-06-01
影响因子：
13.6
通讯作者：
Sayegh, MH
中科院分区：
文献类型：
--
作者：
Salama, AD;Najafian, N;Sayegh, MH
最近的证据表明，在啮齿动物和健康的人类受试者中存在限制免疫反应的专业调节细胞群。然而，它们在疾病状态中的作用仍不清楚。一部分肾移植受者没有表现出对他们的不匹配的供体来源的HLA-DR抗原的体外反应性，因此假设这可能是由于这样的调节细胞。在一家机构对23例肾移植受者进行了队列研究。在无急性排斥史的患者中，15例患者中有6例（40%）表现出CD 25（+）细胞对错配HLA-DR同种异体肽的调节作用。相比之下，只有1/8（12.5%）的急性排斥反应的历史表现出调节。有趣的是，如果根据对错配同种异体肽的初始体外免疫应答对患者测定进行分层，8（47.1%）的17例患者检测具有低别肽反应性（同种异体反应性T细胞频率低于60/百万）证实了CD 25（+）细胞对间接途径同种异体反应的调节，而8例高应答者（频率大于60/百万）中0例未显示这种调节（χ 2检验P < 0.05）。调节细胞存在于循环中，早在移植后3个月，并持续数年，尽管常规的免疫抑制。此外，用抗IL-2 R mAb诱导处理不能阻止这些调节性CD 25（+）细胞的发育。来自两名患者的数据表明，这些细胞也可能在预防表位转移中发挥作用，这与导致慢性排斥的持续免疫激活有关，并且给定患者的调节丧失可能先于排斥发作。
Recent evidence suggests that a population of professional regulatory cells, which limit immune responsiveness, exist in rodents and healthy human subjects. However, their role in disease states remains unclear. A proportion of renal transplant recipients do not demonstrate in vitro reactivity toward their mismatched donor-derived HLA-DR antigens; it was therefore hypothesized that this may be due to such regulatory cells. A cohort of 23 renal transplant recipients was studied at a single institution. In patients with no history of acute rejection, 6 (40%) of 15 demonstrated regulation toward the mismatched HLA-DR allopeptides by CD25(+) cells. By contrast, only one (12.5%) in eight of those with a history of acute rejection demonstrated regulation. Interestingly, if the patient assays were stratified according to initial in vitro immune responsiveness toward the mismatched allopeptides, 8 (47.1%) of 17 of patient assays with low allopeptide responsiveness (alloreactive T cell frequencies less than 60/million) demonstrated regulation of indirect pathway alloresponses by CD25(+) cells, whereas 0 of 8 with higher responses (frequencies greater than 60/million) demonstrated no such regulation (P < 0.05 by chi(2) test). The regulatory cells are present in the circulation as early as 3 mo after transplantation and persist for a number of years, despite conventional immunosuppression. Furthermore, induction treatment with anti-IL-2R mAb did not prevent the development of these regulatory CD25(+) cells. Data from two patients suggest that these cells may also play a role in preventing epitope shifting, implicated in the ongoing immune activation contributing to chronic rejection, and that loss of regulation in a given patient may precede an episode of rejection.