End-stage renal failure and regulatory activities of CD4+CD25bright+FoxP3+ T-cells
End-stage renal failure and regulatory activities of CD4+CD25bright+FoxP3+ T-cells
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DOI：
10.1093/ndt/gfp005
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发表时间：
2009-06-01
影响因子：
6.1
通讯作者：
Baan, Carla C.
中科院分区：
文献类型：
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作者：
Hendrikx, Thijs K.;van Gurp, Eveline A. F. J.;Baan, Carla C.
背景终末期肾衰竭患者的防御性免疫系统在多个层面受损。这种免疫功能不全的状态与免疫系统的持续激活有关。对这种激活状态的另一种解释可能是CD 4（+）CD 25（bright+）FoxP 3（+）调节性T细胞功能紊乱。采用流式细胞术、RT-PCR和混合淋巴细胞反应对80例终末期肾功能衰竭患者和17例健康对照者外周血调节性T细胞的表型和功能进行了研究。患者正在接受血液透析（N = 40）、腹膜透析（N = 26）或尚未接受透析治疗（N = 14）。后者肾小球滤过率< 20 ml/min/ 1.73 m2。患者PBMC中基础IL-2 mRNA水平较高（与健康对照相比，P = 0.0002）。CD 4（+）CD 25（亮+）T细胞的绝对数量在患者中较低（与健康对照相比P < 0.05）。此外，同种异体刺激后患者PBMC的增殖受损（与健康对照相比，P < 0.0001）。CD 4（+）CD 25（亮+）T细胞的调节功能在直接同种异体识别的情况下被确定。首先，从患者PBMC中去除CD 25（亮+）细胞对增殖的影响很低。其次，CD 25（亮+）细胞与CD 25（阴性/暗淡）细胞（1：10比例）共培养显示调节功能受损（与健康对照组相比P < 0.001），这在透析患者中尤其明显。FOXP 3 mRNA水平在刺激后也较低（与健康对照相比P = 0.0002）。与以前的研究一致，我们观察到终末期肾功能衰竭患者的免疫系统过度激活，但功能受损。现在看来，在这种情况下，CD 4（+）CD 25（亮+）FoxP 3（+）T细胞的调节也受损。
Background. The defensive immune system in patients with end-stage renal failure is impaired at multiple levels. This state of immune incompetence is associated with continuous activation of the immune system. An additional explanation for this state of activation may be the disturbed function of CD4(+)CD25(bright+)FoxP3(+) regulatory T-cells.Methods. The phenotype and function of peripheral regulatory T-cells from patients with end-stage renal failure (N = 80) and healthy controls (N = 17) was studied by flow cytometry, RT-PCR and mixed lymphocyte reaction. Patients were on haemodialysis (N = 40), peritoneal dialysis (N = 26) or not treated with dialysis yet (N = 14). The latter group had a glomerular filtration rate of < 20 ml/min/ 1.73 m(2).Results. The basal IL-2 mRNA level was high in patient-PBMC (P = 0.0002 versus healthy controls). The absolute number of CD4(+)CD25(bright+) T-cells was low in patients (P < 0.05 versus healthy controls). Furthermore, proliferation of patient-PBMC upon allogeneic stimulation was impaired (P < 0.0001 versus healthy controls). The regulatory function of CD4(+)CD25(bright+) T-cells was determined in the setting of direct allorecognition. First, the effect of depletion of CD25(bright+) cells from patient-PBMC on proliferation was low. Second, co-culture of CD25(bright+) cells with CD25(neg/dim) cells (1:10 ratio) showed impaired regulatory function (P < 0.001 versus healthy controls), which was especially pronounced in patients on dialysis. The FOXP3 mRNA level was also low upon stimulation (P = 0.0002 versus healthy controls).Conclusions. In line with previous studies, we observed an overactivated but functionally compromised immune system in patients with end-stage renal failure. It now appears that in this setting, regulation by CD4(+)CD25(bright+)FoxP3(+) T-cells is also impaired.