Dijke I Esmé, Korevaar Sander S, Caliskan Kadir, Balk Aggie H M M, Maat Alex P W M, Weimar Willem, Baan Carla C
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Transplantation. 2009 Apr 27;87(8):1191-200. doi: 10.1097/TP.0b013e31819ec2fb.
CD4CD25FoxP3 regulatory T cells are suppressors of antigen-activated immune reactivity. Here, we assessed the clinically relevant role of these cells in the control of immune responses directed to a transplanted heart.
We investigated the phenotype and function of peripheral CD4CD25FoxP3 T cells in heart transplant patients free from acute rejections (n=9) and in rejectors (n=12) before and during acute cellular rejection.
Between rejectors and nonrejectors, the proportion of CD4CD25 T cells and of FoxP3 cells within this population was comparable. Yet, CD4CD25FoxP3 T cells of rejectors had a higher CD127 expression than those of nonrejectors (P<0.0001). Depletion of CD4CD25 T cells from peripheral blood mononuclear cells increased the antidonor proliferative response of both nonrejectors (P=0.0005) and rejectors (P=0.03). In rejectors, however, only a 2-fold increase was measured, whereas the nonrejectors' response became 14 times higher (P=0.002). Reconstitution of CD4CD25 T cells only suppressed the overall antidonor proliferative response of CD25 responder cells of nonrejectors significantly (P=0.001). Moreover, the percentage inhibition of the response was higher in nonrejectors than in rejectors (P=0.02). Analyses of pretransplant samples revealed that CD4CD25 T cells of rejectors already had a lower suppressive capacity than those of nonrejectors before transplantation (P=0.04).
CD4CD25FoxP3 T cells of heart transplant patients who experience acute rejection had an up-regulated CD127 expression and an inadequate regulatory function compared with those of nonrejecting patients. Our observations suggest that the function of circulating CD4CD25FoxP3 regulatory T cells may be pivotal for the prevention of acute cellular rejection after clinical heart transplantation.
CD4CD25FoxP3调节性T细胞是抗原激活的免疫反应的抑制因子。在此，我们评估了这些细胞在控制针对移植心脏的免疫反应中的临床相关作用。
我们研究了心脏移植患者外周血CD4CD25FoxP3 T细胞的表型和功能，这些患者在急性排斥反应期之前和期间均无急性排斥反应（n = 9）以及发生排斥反应的患者（n = 12）。
在发生排斥反应的患者和未发生排斥反应的患者之间，该群体中CD4CD25 T细胞和FoxP3细胞的比例相当。然而，发生排斥反应的患者的CD4CD25FoxP3 T细胞的CD127表达高于未发生排斥反应的患者（P<0.0001）。从外周血单核细胞中去除CD4CD25 T细胞会增加未发生排斥反应的患者（P = 0.0005）和发生排斥反应的患者（P = 0.03）的抗供体增殖反应。然而，在发生排斥反应的患者中，仅检测到2倍的增加，而未发生排斥反应的患者的反应增加了14倍（P = 0.002）。重新引入CD4CD25 T细胞仅显著抑制了未发生排斥反应的患者的CD25应答细胞的总体抗供体增殖反应（P = 0.001）。此外，未发生排斥反应的患者的反应抑制百分比高于发生排斥反应的患者（P = 0.02）。对移植前样本的分析显示，发生排斥反应的患者的CD4CD25 T细胞在移植前的抑制能力就已经低于未发生排斥反应的患者（P = 0.04）。
与未发生排斥反应的患者相比，经历急性排斥反应的心脏移植患者的CD4CD25FoxP3 T细胞的CD127表达上调且调节功能不足。我们的观察结果表明，循环中的CD4CD25FoxP3调节性T细胞的功能可能对临床心脏移植后预防急性细胞排斥反应至关重要。
