Department of Surgery, Fourth Affiliated Hospital, China Medical University, Shenyang, China.
Surgery. 2011 Mar;149(3):336-46. doi: 10.1016/j.surg.2010.08.012. Epub 2010 Sep 26.
We have demonstrated previously that CD4(+)CD25(+) regulatory T cells (Treg) are important for spontaneous hepatic allograft tolerance. In this study, we examine the role of Treg in cardiac allograft acceptance induced by blockade of the CD40-CD40L pathway.
A heterotopic heart transplant model of major histocompatibility complex-mismatched mice was performed. Expression of forkhead/winged helix transcription factor (FoxP3) and/or the number of CD4(+)CD25(+) T cells in allografts and spleens were examined. The effect of Treg from the recipient or the donor on the induction and maintenance of long-term allograft survival was determined. Histologic analyses were also performed. The effects of Treg on CD4(+) and CD8(+) T cells were assessed.
The levels of FoxP3 and/or CD4(+)CD25(+) T cells increased in long-surviving allografts and spleens. Depletion of Treg in the recipients but not the donors before transplantation caused rejection. Histologic analyses of allografts with Treg depletion showed extensive leukocyte infiltration and tissue destruction. However, delayed depletion of Treg in long-surviving recipients did not shorten their survival. Treg depletion increased the function of CD4(+) and CD8(+) T cells.
Treg in the recipient but not in the donor is essential for long-term survival induced by CD40-CD40L blockade by inhibiting the function of CD4(+) and CD8(+) T cells; however, Treg are not important for maintenance. Both allograft and spleen are critical for induction of successful long-term survival.
我们之前已经证明，CD4(+)CD25(+)调节性 T 细胞（Treg）对于自发性肝移植耐受至关重要。在这项研究中，我们研究了 Treg 在阻断 CD40-CD40L 通路诱导的心脏同种异体移植物接受中的作用。
进行了主要组织相容性复合物错配小鼠的异位心脏移植模型。检查了同种异体移植物和脾脏中叉头/翼状螺旋转录因子（FoxP3）的表达和/或 CD4(+)CD25(+)T 细胞的数量。确定了来自受者或供者的 Treg 对诱导和维持长期同种异体移植物存活的影响。还进行了组织学分析。评估了 Treg 对 CD4(+)和 CD8(+)T 细胞的影响。
FoxP3 和/或 CD4(+)CD25(+)T 细胞的水平在长期存活的同种异体移植物和脾脏中增加。在移植前耗尽受者而不是供者的 Treg 会导致排斥。用 Treg 耗尽的同种异体移植物的组织学分析显示广泛的白细胞浸润和组织破坏。然而，在长期存活的受者中延迟耗尽 Treg 并没有缩短其存活时间。Treg 耗竭增加了 CD4(+)和 CD8(+)T 细胞的功能。
受者而不是供者中的 Treg 对于通过阻断 CD40-CD40L 诱导的长期存活是必需的，通过抑制 CD4(+)和 CD8(+)T 细胞的功能；然而，Treg 对于维持不重要。同种异体移植物和脾脏对于诱导成功的长期存活都是至关重要的。
