Dijke I Esmé, Velthuis Jurjen H L, Caliskan Kadir, Korevaar Sander S, Maat Alex P W M, Zondervan Pieter E, Balk Aggie H M M, Weimar Willem, Baan Carla C
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
Transplantation. 2007 Jun 15;83(11):1477-84. doi: 10.1097/01.tp.0000264997.53153.8b.
Regulatory FOXP3+ T cells control immune responses of effector T cells. However, whether these cells regulate antidonor responses in the graft of cardiac allograft patients is unknown. Therefore, we analyzed the gene expression profiles of regulatory and effector T-cell markers during immunological quiescence and acute rejection.
Quantitative real-time polymerase chain reaction was used to analyze mRNA expression levels in time-zero specimens (n=24) and endomyocardial biopsies (EMB; n=72) of cardiac allograft patients who remained free from rejection (nonrejectors; n=12) and patients with at least one histologically proven acute rejection episode (rejectors; International Society for Heart and Lung Transplantation [ISHLT] rejection grade>2; n=12).
For all analyzed regulatory and effector T-cell markers, mRNA expression levels were increased in biopsies taken after heart transplantation compared with those in time-zero specimens. Posttransplantation, the FOXP3 mRNA levels were higher in EMB assigned to a higher ISHLT rejection grade than the biopsies with grade 0: the highest mRNA levels were detected in the rejection biopsies (rejection grade>2; P=0.003). In addition, the mRNA levels of CD25, glucocorticoid-induced TNF receptor family-related gene, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, and granzyme B were also significantly higher in rejecting EMB than in nonrejecting EMB (rejection grade<or=2). This increase in expression levels in relation to the histological rejection grade was only observed in patients who developed an acute rejection episode; the mRNA levels of nonrejectors remained stable irrespective of ISHLT rejection grade.
These observations suggest that, after clinical heart transplantation, FOXP3+ T cells do not prevent acute rejection, but rather are a response to antidonor effector T-cell activity.
调节性FOXP3⁺ T细胞控制效应T细胞的免疫反应。然而，这些细胞是否调节心脏移植患者移植物中的抗供体反应尚不清楚。因此，我们分析了免疫静止期和急性排斥反应期间调节性和效应性T细胞标志物的基因表达谱。
采用定量实时聚合酶链反应分析心脏移植患者零时间标本（n = 24）和心内膜心肌活检标本（EMB；n = 72）中mRNA表达水平，这些患者包括未发生排斥反应的患者（非排斥者；n = 12）和至少有一次组织学证实的急性排斥反应发作的患者（排斥者；国际心肺移植学会[ISHLT]排斥分级>2；n = 12）。
对于所有分析的调节性和效应性T细胞标志物，与零时间标本相比，心脏移植后活检标本中的mRNA表达水平升高。移植后，ISHLT排斥分级较高的EMB中FOXP3 mRNA水平高于0级活检标本：排斥活检标本（排斥分级>2；P = 0.003）中检测到最高的mRNA水平。此外，排斥性EMB中CD25、糖皮质激素诱导的TNF受体家族相关基因、细胞毒性T淋巴细胞相关抗原4、白细胞介素-2和颗粒酶B的mRNA水平也显著高于非排斥性EMB（排斥分级≤2）。仅在发生急性排斥反应发作的患者中观察到与组织学排斥分级相关的表达水平升高；无论ISHLT排斥分级如何，非排斥者的mRNA水平保持稳定。
这些观察结果表明，临床心脏移植后，FOXP3⁺ T细胞不能预防急性排斥反应，而是对抗供体效应T细胞活性的一种反应。
