Kidney-induced systemic tolerance of heart allografts in mice.
Kidney-induced systemic tolerance of heart allografts in mice.
复制标题
小鼠心脏同种异体移植物的肾脏诱导的系统耐受性。
DOI：
10.1172/jci.insight.139331
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发表时间：
2020
期刊：
影响因子：
8
通讯作者：
Alessandrini,Alessandro
中科院分区：
文献类型：
--
作者：
Yang,Chao;Ge,Jifu;Rosales,Ivy;Yuan,Qing;Szuter,Edward;Acheampong,Ellen;Russell,PaulS;Madsen,JorenC;Colvin,RobertB;Alessandrini,Alessandro
在猪和非人灵长类动物中，同种异体肾脏移植可以诱导对同种异体心脏移植的耐受性，从而导致其长期无免疫抑制的存活。我们将这种现象称为肾诱导的心脏异体移植耐受（KICAT）。在这项研究中，我们建立了KICAT的小鼠模型来确定潜在的细胞/分子机制。在这里，我们发现C57BL/6受体自发接受的DBA/2J肾脏诱导了全身耐受，导致DBA/2J心脏移植长期接受，而不是第三方心脏移植。心脏的全身耐受状态在肾移植后2周建立，此后不再需要移植同种异体肾。这些小鼠体内Foxp3+ T细胞的缺失导致了同种异体心脏移植物的排斥反应，这表明KICAT依赖于Treg功能。同种异体肾脏移植和同种异体心脏移植的接受不需要胸腺。综上所述，这些数据表明，同种异体肾脏移植通过Foxp3细胞诱导了对同种异体心脏移植的全身、供体特异性耐受，并且这种耐受不依赖于胸腺和同种异体肾脏移植的持续存在。该实验系统将促进对肾脏耐受机制的进一步了解。
In swine and nonhuman primates, kidney allografts can induce tolerance of heart allografts, leading to their long-term, immunosuppression-free survival. We refer to this phenomenon as kidney-induced cardiac allograft tolerance (KICAT). In this study, we have developed a murine model for KICAT to determine the underlining cellular/molecular mechanisms. Here, we show that spontaneously accepted DBA/2J kidneys in C57BL/6 recipients induce systemic tolerance that results in the long-term acceptance of DBA/2J heart allografts but not third-party cardiac allografts. The state of systemic tolerance of hearts was established 2 weeks after transplantation of the kidney, after which time, the kidney allograft is no longer required. Depletion of Foxp3+ T cells from these mice precipitated rejection of the heart allografts, indicating that KICAT is dependent on Treg function. Acceptance of kidney allografts and cotransplanted heart allografts did not require the thymus. In conclusion, these data show that kidney allografts induce systemic, donor-specific tolerance of cardiac allografts via Foxp3 cells, and that tolerance is independent of the thymus and continued presence of the kidney allograft. This experimental system should promote increased understanding of the tolerogenic mechanisms of the kidney.