Barlage S, Hauser I A, Elbracht R, Abletshauser C, Schmieder R E, Weidinger G, Lackner K J, Rothe G, Schmitz G
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
J Biol Regul Homeost Agents. 2005 Jul-Dec;19(3-4):159-68.
Flow cytometric T-cell analysis is capable of adding valuable information for balancing immunosuppression in transplant recipients as it can take into account individual effects of immunosuppressive drugs on each patient as well as effects of other drugs which may modify the overall immunosuppression. Studies suggest that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ rejection, although the precise mechanism of this effect is unknown. We therefore evaluated the effect of fluvastatin on size and activation of T-cell subpopulations and NK-cell activity in renal transplant recipients. At baseline, the population size of activated (HLA-DR+) T-cells was negatively correlated to serum HDL cholesterol suggesting an increased T-cell activation at low HDL levels. Fluvastatin treatment of a hypercholesterolemic group of patients for two months significantly decreased the LDL cholesterol. A longitudinal analysis revealed a relative increase in non-MHC restricted cytotoxic T-cells (CD3+/CD16+ or CD56+) over time which was significantly attenuated in fluvastatin treated patients but not in normocholesterolemic controls. Moreover, a relative decrease of activated MHC class I-restricted cytotoxic CD8+ T-cells was only observed upon fluvastatin treatment. NK-cell number and activity did not differ between groups. In summary, fluvastatin treatment of hypercholesterolemic renal transplant recipients is associated with a specific modulation of T-cells exerting cytotoxic effector functions.
流式细胞术T细胞分析能够为平衡移植受者的免疫抑制提供有价值的信息,因为它可以考虑免疫抑制药物对每个患者的个体影响以及其他可能改变整体免疫抑制的药物的影响。研究表明,HMG-CoA还原酶抑制剂(他汀类药物)可降低器官排斥反应的发生率,尽管这种作用的确切机制尚不清楚。因此,我们评估了氟伐他汀对肾移植受者T细胞亚群大小和活化以及NK细胞活性的影响。在基线时,活化的(HLA-DR +)T细胞群体大小与血清高密度脂蛋白胆固醇呈负相关,表明在低高密度脂蛋白水平下T细胞活化增加。对一组高胆固醇血症患者进行两个月的氟伐他汀治疗可显著降低低密度脂蛋白胆固醇。纵向分析显示,随着时间的推移,非MHC限制性细胞毒性T细胞(CD3 + / CD16 +或CD56 +)相对增加,这在氟伐他汀治疗的患者中显著减弱,但在正常胆固醇血症对照组中未减弱。此外,仅在氟伐他汀治疗后才观察到活化的MHC I类限制性细胞毒性CD8 + T细胞相对减少。各组之间NK细胞数量和活性没有差异。总之,对高胆固醇血症肾移植受者进行氟伐他汀治疗与发挥细胞毒性效应功能的T细胞的特异性调节有关。