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血液透析影响 CD4 阳性 T 淋巴细胞的表型和增殖。

Hemodialysis affects phenotype and proliferation of CD4-positive T lymphocytes.

机构信息

Department of Pathophysiology, Medical University of Gdańsk, Dębinki 7, 80-211, Gdańsk, Poland.

出版信息

J Clin Immunol. 2012 Feb;32(1):189-200. doi: 10.1007/s10875-011-9603-x. Epub 2011 Oct 13.

Abstract

CD4(+) T lymphocytes of patients with chronic kidney disease (CKD) are characterized by reduced levels of crucial surface antigens and changes in the cell cycle parameters. Recombinant human erythropoietin (rhEPO) normalizes their altered phenotype and proliferative capacity. Mechanisms leading to the deficient responses of T lymphocytes are still not clear but it is postulated that immunological changes are deepened by hemodialysis (HD). Study of activation parameters of CD4(+) T lymphocytes in hemodialyzed and predialysis CKD patients could bring insight into this problem. Two groups of patients, treated conservatively (predialysis, PD) and hemodialyzed (HD), as well as healthy controls, were included into the study; neither had received rhEPO. Proportions of main CD4(+)CD28(+), CD4(+)CD25(+), CD4(+)CD69(+), CD4(+)CD95(+), and CD4(+)HLA-DR(+) lymphocyte subpopulations and proliferation kinetic parameters were measured with flow cytometry, both ex vivo and in vitro. No differences were seen in the proportions of main CD4(+) lymphocyte subpopulations (CD4(+)CD28(+), CD4(+)CD25(+), CD4(+)HLA-DR(+), CD4(+)CD69(+), CD4(+)CD95(+)) between all examined groups ex vivo. CD4(+) T lymphocytes of HD patients exhibited significantly decreased expression of co-stimulatory molecule CD28 and activation markers CD25 and CD69 after stimulation in vitro when compared with PD patients and healthy controls. HD patients showed also decreased percentage of CD4(+)CD28(+) lymphocytes proliferating in vitro; these cells presented decreased numbers of finished divisions after 72 h of stimulation in vitro and had longer G0→G1 time when compared to healthy controls. CD4(+) T lymphocytes of PD patients and healthy controls were characterized by similar cell cycle parameters. Our study shows that repeated hemodialysis procedure influences phenotype and proliferation parameters of CD4(+) T lymphocytes.

摘要

慢性肾脏病(CKD)患者的 CD4(+)T 淋巴细胞表现为关键表面抗原水平降低和细胞周期参数改变。重组人促红细胞生成素(rhEPO)可使异常表型和增殖能力正常化。导致 T 淋巴细胞反应不足的机制尚不清楚,但据推测,免疫变化因血液透析(HD)而加深。研究血液透析和未透析 CKD 患者 CD4(+)T 淋巴细胞的激活参数可以深入了解这一问题。本研究纳入了两组患者,一组接受保守治疗(未透析,PD),另一组接受血液透析(HD),以及健康对照组,均未接受 rhEPO 治疗。使用流式细胞术测量了主要 CD4(+)CD28(+)、CD4(+)CD25(+)、CD4(+)CD69(+)、CD4(+)CD95(+)和 CD4(+)HLA-DR(+)淋巴细胞亚群的比例和增殖动力学参数,包括体外和体内。所有检查组的主要 CD4(+)淋巴细胞亚群(CD4(+)CD28(+)、CD4(+)CD25(+)、CD4(+)HLA-DR(+)、CD4(+)CD69(+)、CD4(+)CD95(+))比例在体外均无差异。与 PD 患者和健康对照组相比,HD 患者的 CD4(+)T 淋巴细胞在体外刺激后,共刺激分子 CD28 和激活标志物 CD25 和 CD69 的表达显著降低。HD 患者体外增殖的 CD4(+)CD28(+)淋巴细胞比例也降低;与健康对照组相比,这些细胞在体外刺激 72 小时后完成的分裂数量减少,并且 G0→G1 时间更长。PD 患者和健康对照组的 CD4(+)T 淋巴细胞具有相似的细胞周期参数。我们的研究表明,反复血液透析程序会影响 CD4(+)T 淋巴细胞的表型和增殖参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa6/3276768/1a3e3c203954/10875_2011_9603_Fig1_HTML.jpg

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