San Segundo D, Fábrega E, López-Hoyos M, Pons F
Servicios Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain.
Transplant Proc. 2007 Sep;39(7):2290-2. doi: 10.1016/j.transproceed.2007.07.076.
In solid organ transplantation, most efforts are directed to achieve a state of tolerance and reduce the immunosuppressive load. Since the liver is thought to be more tolerogenic than other grafts, we examined the impact of various immunosuppressant regimens on induction of CD4+CD25(high)FOXP3+ regulatory T cells (Tregs).
We divided 35 liver transplant recipients with stable function and free of rejection episodes for at least 8 years into two main groups according to the blood levels of calcineurin inhibitors (CNIs) at the time of the study: 15 patients showing high concentrations of either cyclosporine or FK506 (high CNI: cyclosporine >80 ng/mL or FK506 >6 ng/mL) and another 20 patients with low levels (low CNI). Thirty-eight age-matched healthy subjects were used as normal controls.
Circulating T cells of a regulatory phenotype (CD4+CD25(high)FoxP3+) were decreased in peripheral blood of liver transplant recipients compared with healthy donors. Importantly, those patients with high CNI demonstrated significantly lower levels of Tregs compared with those with low CNI. Furthermore, low CNI recipients showed no significant difference from healthy donors.
A high load of immunosuppression may hamper the induction of tolerance in liver transplantation through interference with induction of Tregs in stable liver transplant recipients. Thus, quantification of blood Tregs may help to decide whether to lower immunosuppression.
在实体器官移植中，大多数努力都致力于实现免疫耐受状态并降低免疫抑制负荷。由于肝脏被认为比其他移植物更具免疫耐受性，我们研究了各种免疫抑制方案对诱导CD4 + CD25（高）FOXP3 +调节性T细胞（Tregs）的影响。
我们根据研究时钙调神经磷酸酶抑制剂（CNIs）的血药浓度，将35例肝功能稳定且至少8年无排斥反应的肝移植受者分为两个主要组：15例患者环孢素或FK506浓度高（高CNI组：环孢素> 80 ng/mL或FK506> 6 ng/mL），另外20例患者浓度低（低CNI组）。38名年龄匹配的健康受试者作为正常对照。
与健康供者相比，肝移植受者外周血中具有调节表型（CD4 + CD25（高）FoxP3 +）的循环T细胞减少。重要的是，高CNI组患者的Tregs水平明显低于低CNI组患者。此外，低CNI组受者与健康供者无显著差异。
高剂量的免疫抑制可能会通过干扰稳定肝移植受者中Tregs的诱导来阻碍肝移植中的耐受诱导。因此，定量血液中的Tregs可能有助于决定是否降低免疫抑制。
