San Segundo D, Ruiz J C, Fernández-Fresnedo G, Izquierdo M, Gómez-Alamillo C, Cacho E, Benito M J, Rodrigo E, Palomar R, López-Hoyos M, Arias M
Servicios de Inmunología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Transplant Proc. 2006 Oct;38(8):2391-3. doi: 10.1016/j.transproceed.2006.08.081.
Immunosuppression, although crucial for short-term management, has been described in renal transplantation to be a major hurdle for long-term graft survival. Efforts have been directed at achieving a true state of allotolerance, thereby reducing the load of immunosuppression. Recently, increased frequencies of CD4(+)CD25(high) regulatory T cells (Tregs) have been described as an additional mechanism to induce alloimmune tolerance.
We assessed 64 renal transplant recipients with stable renal function for at least 1 year, divided into two groups: one composed of patients receiving rapamycin but not calcineurin inhibitors (CNIs), and another, of those receiving CNIs but not rapamycin.
We demonstrated that T cells with a regulatory phenotype were decreased in peripheral blood of renal transplant recipients under CNI therapy compared to those who were CNI-free. The Tregs in our patients showed a modest association with renal function as measured by the delta serum creatinine, which was not significant.
CNIs, but not rapamycin, reduce the frequencies of circulating Tregs in renal transplant recipients. The use of rapamycin might be further exploited in strategies reducing immunosuppression in renal transplantation. Furthermore, quantification of blood Tregs may be a suitable tool to identify those recipients who are candidates for reducing immunosuppression.
免疫抑制虽然对短期治疗至关重要,但在肾移植中已被描述为长期移植物存活的主要障碍。人们一直致力于实现真正的同种耐受状态,从而减少免疫抑制的负担。最近,CD4(+)CD25(高)调节性T细胞(Tregs)频率的增加被描述为诱导同种免疫耐受的另一种机制。
我们评估了64例肾功能稳定至少1年的肾移植受者,分为两组:一组由接受雷帕霉素但未接受钙调神经磷酸酶抑制剂(CNIs)的患者组成,另一组由接受CNIs但未接受雷帕霉素的患者组成。
我们证明,与未接受CNI治疗的肾移植受者相比,接受CNI治疗的肾移植受者外周血中具有调节表型的T细胞减少。我们患者中的Tregs与通过血清肌酐变化测量的肾功能有适度关联,但不显著。
CNIs而非雷帕霉素可降低肾移植受者循环Tregs的频率。雷帕霉素的使用可能在减少肾移植免疫抑制的策略中得到进一步应用。此外,血液Tregs的定量可能是识别那些适合减少免疫抑制的受者的合适工具。